{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:49:41Z","timestamp":1791244181588,"version":"4.1.0"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":33,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"L.V. receives research grants from J&J, ViiV Healthcare and Gilead Sciences"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    HIV persistence in reservoirs despite antiretroviral therapy (ART) is a barrier to a permanent cure. We present the affinity-enhanced TCR bispecific IMC-M113V as a potential therapeutic for targeted HIV reservoir elimination. Preclinical studies demonstrate that IMC-M113V redirects T cells towards cells expressing the variable viral peptide, Gag\n                    <jats:sub>77-85,<\/jats:sub>\n                    presented by HLA-A*02:01 at low copy number, without binding to HIV-negative cells. Here, we conduct a first-in-human, open-label single ascending dose study of IMC-M113V (1.6-15\u2009\u00b5g) in twelve HLA-A*02:01-positive males living with HIV on suppressive ART (EudraCT number 2021-002008-11). Participants receive one intravenous infusion of IMC-M113V on Day 1 and are monitored through Day 29 to evaluate safety, tolerability (primary endpoints) and pharmacodynamic (PD) activity (secondary endpoint). IMC-M113V is well tolerated and not associated with any serious adverse event. PD activity is dose-dependent and strongest in participants with highly IMC-M113V-sensitive Gag\n                    <jats:sub>77-85<\/jats:sub>\n                    variant sequences. Thus, we provide a promising foundation to evaluate multiple and higher doses of IMC-M113V as a strategy for achieving ART-free virological control.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-68833-2","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T06:44:17Z","timestamp":1769841857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Safety and biologic activity of a bispecific T cell receptor targeting HIV Gag in males living with HIV: a first-in-human trial"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8600-1631","authenticated-orcid":false,"given":"Linos","family":"Vandekerckhove","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-8019","authenticated-orcid":false,"given":"Julie","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4719-6827","authenticated-orcid":false,"given":"Borja","family":"Mora-Peris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7187-0367","authenticated-orcid":false,"given":"Jordi","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine D.","family":"Allard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison J.","family":"Uriel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Moreno Guill\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Boffito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2844-1612","authenticated-orcid":false,"given":"Frank A.","family":"Post","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Estrada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9975-407X","authenticated-orcid":false,"given":"Beatriz","family":"Mothe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-3012","authenticated-orcid":false,"given":"Mareva","family":"Delporte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3174-482X","authenticated-orcid":false,"given":"Adel","family":"Benlahrech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haseeb","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1823-4136","authenticated-orcid":false,"given":"James","family":"Clubley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-8189","authenticated-orcid":false,"given":"Agatha","family":"Treveil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Chamberlain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4353-3738","authenticated-orcid":false,"given":"Miriam","family":"Hock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Wustner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Moureau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9931-3706","authenticated-orcid":false,"given":"Andrew D.","family":"Whale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zo\u00eb","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen K.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehmia","family":"Titanji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Dorrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-7583","authenticated-orcid":false,"given":"Sarah","family":"Fidler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"68833_CR1","doi-asserted-by":"publisher","unstructured":"Armani-Tourret, M. et al. Immune targeting of HIV-1 reservoir cells: a path to elimination strategies and cure. Nat. Rev. Microbiol. https:\/\/doi.org\/10.1038\/s41579-024-01010-8 (2024).","DOI":"10.1038\/s41579-024-01010-8"},{"key":"68833_CR2","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1097\/COH.0000000000000851","volume":"19","author":"R Banga","year":"2024","unstructured":"Banga, R. & Perreau, M. The multifaceted nature of HIV tissue reservoirs. Curr. Opin. HIV AIDS 19, 116\u2013123 (2024).","journal-title":"Curr. Opin. HIV AIDS"},{"key":"68833_CR3","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1056\/NEJMoa0802905","volume":"360","author":"G H\u00fctter","year":"2009","unstructured":"H\u00fctter, G. et al. Long-term control of HIV by CCR5 delta32\/Delta32 stem-cell transplantation. N. Engl. J. Med. 360, 692\u2013698 (2009).","journal-title":"N. Engl. J. Med."},{"key":"68833_CR4","doi-asserted-by":"publisher","first-page":"2791","DOI":"10.1182\/blood-2010-09-309591","volume":"117","author":"K Allers","year":"2011","unstructured":"Allers, K. et al. Evidence for the cure of HIV infection by CCR5\u039432\/\u039432 stem cell transplantation. Blood 117, 2791\u20132799 (2011).","journal-title":"Blood"},{"key":"68833_CR5","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1038\/s41586-019-1027-4","volume":"568","author":"RK Gupta","year":"2019","unstructured":"Gupta, R. K. et al. HIV-1 remission following CCR5\u039432\/\u039432 haematopoietic stem-cell transplantation. Nature 568, 244\u2013248 (2019).","journal-title":"Nature"},{"key":"68833_CR6","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41591-023-02213-x","volume":"29","author":"B-EO Jensen","year":"2023","unstructured":"Jensen, B.-E. O. et al. In-depth virological and immunological characterization of HIV-1 cure after CCR5\u039432\/\u039432 allogeneic hematopoietic stem cell transplantation. Nat. Med. 29, 583\u2013587 (2023).","journal-title":"Nat. Med."},{"key":"68833_CR7","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/j.cell.2023.02.030","volume":"186","author":"J Hsu","year":"2023","unstructured":"Hsu, J. et al. HIV-1 remission and possible cure in a woman after haplo-cord blood transplant. Cell 186, 1115\u20131126.e8 (2023).","journal-title":"Cell"},{"key":"68833_CR8","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1038\/s41591-021-01590-5","volume":"27","author":"SG Deeks","year":"2021","unstructured":"Deeks, S. G. et al. Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021. Nat. Med. 27, 2085\u20132098 (2021).","journal-title":"Nat. Med."},{"key":"68833_CR9","doi-asserted-by":"publisher","first-page":"103118","DOI":"10.1016\/j.ebiom.2020.103118","volume":"62","author":"BA Woldemeskel","year":"2020","unstructured":"Woldemeskel, B. A., Kwaa, A. K. & Blankson, J. N. Viral reservoirs in elite controllers of HIV-1 infection: Implications for HIV cure strategies. EBioMedicine 62, 103118 (2020).","journal-title":"EBioMedicine"},{"key":"68833_CR10","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1038\/s41591-022-02060-2","volume":"28","author":"L Bail\u00f3n","year":"2022","unstructured":"Bail\u00f3n, L. et al. Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial. Nat. Med. 28, 2611\u20132621 (2022).","journal-title":"Nat. Med."},{"key":"68833_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-42888-3","volume":"13","author":"J Kopycinski","year":"2023","unstructured":"Kopycinski, J. et al. Therapeutic vaccination following early antiretroviral therapy elicits highly functional T cell responses against conserved HIV-1 regions. Sci. Rep. 13, 17155 (2023).","journal-title":"Sci. Rep."},{"key":"68833_CR12","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1097\/QCO.0000000000000803","volume":"35","author":"MJ Lee","year":"2022","unstructured":"Lee, M. J., Fidler, S. & Frater, J. Immunotherapeutic approaches to HIV cure and remission. Curr. Opin. Infect. Dis. 35, 31\u201341 (2022).","journal-title":"Curr. Opin. Infect. Dis."},{"key":"68833_CR13","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41586-018-0531-2","volume":"561","author":"P Mendoza","year":"2018","unstructured":"Mendoza, P. et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature 561, 479\u2013484 (2018).","journal-title":"Nature"},{"key":"68833_CR14","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.1038\/s41591-022-02023-7","volume":"28","author":"JD Gunst","year":"2022","unstructured":"Gunst, J. D. et al. Early intervention with 3BNC117 and romidepsin at antiretroviral treatment initiation in people with HIV-1: a phase 1b\/2a, randomized trial. Nat. Med. 28, 2424\u20132435 (2022).","journal-title":"Nat. Med."},{"key":"68833_CR15","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1038\/s41591-023-02547-6","volume":"29","author":"JD Gunst","year":"2023","unstructured":"Gunst, J. D. et al. Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial. Nat. Med. 29, 2547\u20132558 (2023).","journal-title":"Nat. Med."},{"key":"68833_CR16","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/s41586-022-04597-1","volume":"606","author":"C Gaebler","year":"2022","unstructured":"Gaebler, C. et al. Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature 606, 368\u2013374 (2022).","journal-title":"Nature"},{"key":"68833_CR17","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.161698","volume":"7","author":"K Anthony-Gonda","year":"2022","unstructured":"Anthony-Gonda, K. et al. In vivo killing of primary HIV-infected cells by peripheral-injected early memory\u2013enriched anti-HIV duoCAR T cells. JCI Insight 7, e161698 (2022).","journal-title":"JCI Insight"},{"key":"68833_CR18","doi-asserted-by":"publisher","unstructured":"Dashti, A. et al. SMAC mimetic plus triple-combination bispecific HIVxCD3 retargeting molecules in SHIV.C.CH505-infected, antiretroviral therapy-suppressed rhesus macaques. J. Virol. https:\/\/doi.org\/10.1128\/jvi.00793-20 (2020).","DOI":"10.1128\/jvi.00793-20"},{"key":"68833_CR19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217887120","volume":"120","author":"PK Dash","year":"2023","unstructured":"Dash, P. K. et al. CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice. Proc. Natl. Acad. Sci. USA 120, e2217887120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"68833_CR20","doi-asserted-by":"publisher","first-page":"e144486","DOI":"10.1172\/JCI144486","volume":"131","author":"P Tebas","year":"2021","unstructured":"Tebas, P. et al. CCR5-edited CD4 T cells augment HIV-specific immunity to enable post rebound control of HIV replication. J. Clin. Investig. 131, e144486 (2021).","journal-title":"J. Clin. Investig."},{"key":"68833_CR21","doi-asserted-by":"publisher","first-page":"e42","DOI":"10.1016\/S2352-3018(20)30234-4","volume":"8","author":"SR Lewin","year":"2020","unstructured":"Lewin, S. R. et al. Multi-stakeholder consensus on a target product profile for an HIV cure. Lancet HIV 8, e42\u2013e50 (2020).","journal-title":"Lancet HIV"},{"key":"68833_CR22","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1038\/nm.2764","volume":"18","author":"N Liddy","year":"2012","unstructured":"Liddy, N. et al. Monoclonal TCR-redirected tumor cell killing. Nat. Med. 18, 980\u2013987 (2012).","journal-title":"Nat. Med."},{"key":"68833_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-23228-3","volume":"12","author":"Z Wallace","year":"2022","unstructured":"Wallace, Z. et al. Immune mobilising T cell receptors redirect polyclonal CD8+ T cells in chronic HIV infection to form immunological synapses. Sci. Rep. 12, 18366 (2022).","journal-title":"Sci. Rep."},{"key":"68833_CR24","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1056\/NEJMoa2103485","volume":"385","author":"P Nathan","year":"2021","unstructured":"Nathan, P. et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. New Engl. J. Med. 385, 1196\u20131206 (2021).","journal-title":"New Engl. J. Med."},{"key":"68833_CR25","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1002\/hep.31503","volume":"72","author":"JR Fergusson","year":"2020","unstructured":"Fergusson, J. R. et al. Immune-mobilizing monoclonal T cell receptors mediate specific and rapid elimination of hepatitis B-infected cells. Hepatology 72, 1528\u20131540 (2020).","journal-title":"Hepatology"},{"key":"68833_CR26","doi-asserted-by":"publisher","first-page":"100082","DOI":"10.1016\/j.jve.2022.100082","volume":"8","author":"Z Wallace","year":"2022","unstructured":"Wallace, Z., Singh, P. K. & Dorrell, L. Combination strategies to durably suppress HIV-1: soluble T cell receptors. J. Virus Erad. 8, 100082 (2022).","journal-title":"J. Virus Erad."},{"key":"68833_CR27","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1038\/mt.2016.114","volume":"24","author":"H Yang","year":"2016","unstructured":"Yang, H. et al. Elimination of latently HIV-infected cells from antiretroviral therapy-suppressed subjects by engineered immune-mobilizing T-cell receptors. Mol. Ther. 24, 1913\u20131925 (2016).","journal-title":"Mol. Ther."},{"key":"68833_CR28","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1093\/infdis\/jiab121","volume":"224","author":"G Wu","year":"2021","unstructured":"Wu, G. et al. Gag p24 is a marker of human immunodeficiency virus expression in tissues and correlates with immune response. J. Infect. Dis. 224, 1593\u20131598 (2021).","journal-title":"J. Infect. Dis."},{"key":"68833_CR29","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aap9927","volume":"10","author":"SA Yukl","year":"2018","unstructured":"Yukl, S. A. et al. HIV latency in isolated patient CD4+ T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing. Sci. Transl. Med. 10, eaap9927 (2018).","journal-title":"Sci. Transl. Med."},{"key":"68833_CR30","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/S1074-7613(00)80065-5","volume":"10","author":"GB Cohen","year":"1999","unstructured":"Cohen, G. B. et al. The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 10, 661\u2013671 (1999).","journal-title":"Immunity"},{"key":"68833_CR31","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1038\/nm.4113","volume":"22","author":"R Banga","year":"2016","unstructured":"Banga, R. et al. PD-1+ and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat. Med. 22, 754\u2013761 (2016).","journal-title":"Nat. Med."},{"key":"68833_CR32","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.132997","volume":"5","author":"MJ Peluso","year":"2020","unstructured":"Peluso, M. J. et al. Differential decay of intact and defective proviral DNA in HIV-1-infected individuals on suppressive antiretroviral therapy. JCI Insight 5, e132997 (2020).","journal-title":"JCI Insight"},{"key":"68833_CR33","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S1473-3099(18)30647-9","volume":"19","author":"J Hemelaar","year":"2019","unstructured":"Hemelaar, J. et al. Global and regional molecular epidemiology of HIV-1, 1990\u20132015: a systematic review, global survey, and trend analysis. Lancet Infect. Dis. 19, 143\u2013155 (2019).","journal-title":"Lancet Infect. Dis."},{"key":"68833_CR34","doi-asserted-by":"publisher","first-page":"7308","DOI":"10.4049\/jimmunol.176.12.7308","volume":"176","author":"MA Purbhoo","year":"2006","unstructured":"Purbhoo, M. A. et al. Quantifying and imaging NY-ESO-1\/LAGE-1-derived epitopes on tumor cells using high affinity T cell receptors. J Immunol 176, 7308\u20137316 (2006).","journal-title":"J Immunol"},{"key":"68833_CR35","doi-asserted-by":"publisher","first-page":"e0205491","DOI":"10.1371\/journal.pone.0205491","volume":"13","author":"J Harper","year":"2018","unstructured":"Harper, J. et al. An approved in vitro approach to preclinical safety and efficacy evaluation of engineered T cell receptor anti-CD3 bispecific (ImmTAC) molecules. PLoS One 13, e0205491 (2018).","journal-title":"PLoS One"},{"key":"68833_CR36","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.humimm.2007.04.005","volume":"68","author":"M Maiers","year":"2007","unstructured":"Maiers, M., Gragert, L. & Klitz, W. High-resolution HLA alleles and haplotypes in the United States population. Hum. Immunol. 68, 779\u2013788 (2007).","journal-title":"Hum. Immunol."},{"key":"68833_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-06704-4","volume":"15","author":"AW Banjoko","year":"2025","unstructured":"Banjoko, A. W. et al. High resolution class I HLA-A, -B, and -C diversity in Eastern and Southern African populations. Sci. Rep. 15, 23667 (2025).","journal-title":"Sci. Rep."},{"key":"68833_CR38","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1093\/jnci\/89.15.1138","volume":"89","author":"R Simon","year":"1997","unstructured":"Simon, R. et al. Accelerated titration designs for phase I clinical trials in oncology. J. Natl. Cancer Inst. 89, 1138\u20131147 (1997).","journal-title":"J. Natl. Cancer Inst."},{"key":"68833_CR39","doi-asserted-by":"publisher","first-page":"5869","DOI":"10.1158\/1078-0432.CCR-20-1247","volume":"26","author":"MR Middleton","year":"2020","unstructured":"Middleton, M. R. et al. Tebentafusp, A TCR\/Anti-CD3 bispecific fusion protein targeting gp100, potently activated antitumor immune responses in patients with metastatic melanoma. Clin Cancer Res. Off. J. Am. Assoc. Cancer Res. 26, 5869\u20135878 (2020).","journal-title":"Clin Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"68833_CR40","doi-asserted-by":"publisher","unstructured":"Carvajal, R. D. et al. Clinical and molecular response to tebentafusp in previously treated patients with metastatic uveal melanoma: a phase 2 trial. Nat. Med. https:\/\/doi.org\/10.1038\/s41591-022-02015-7 (2022).","DOI":"10.1038\/s41591-022-02015-7"},{"key":"68833_CR41","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2022.2039432","volume":"11","author":"G Leclercq","year":"2022","unstructured":"Leclercq, G. et al. Dissecting the mechanism of cytokine release induced by T-cell engagers highlights the contribution of neutrophils. OncoImmunology 11, 2039432 (2022).","journal-title":"OncoImmunology"},{"key":"68833_CR42","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.3389\/fimmu.2019.01093","volume":"10","author":"NR West","year":"2019","unstructured":"West, N. R. Coordination of immune-stroma crosstalk by IL-6 family cytokines. Front. Immunol. 10, 1093 (2019).","journal-title":"Front. Immunol."},{"key":"68833_CR43","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1038\/s41591-020-1022-1","volume":"26","author":"M Abdel-Mohsen","year":"2020","unstructured":"Abdel-Mohsen, M. et al. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat. Med. 26, 1339\u20131350 (2020).","journal-title":"Nat. Med."},{"key":"68833_CR44","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1038\/nm.1779","volume":"14","author":"A Varela-Rohena","year":"2008","unstructured":"Varela-Rohena, A. et al. Control of HIV-1 immune escape by CD8 T cells expressing enhanced T-cell receptor. Nat. Med. 14, 1390\u20131395 (2008).","journal-title":"Nat. Med."},{"key":"68833_CR45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004010","volume":"10","author":"MF Kearney","year":"2014","unstructured":"Kearney, M. F. et al. Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy. PLoS Pathog. 10, e1004010 (2014).","journal-title":"PLoS Pathog."},{"key":"68833_CR46","doi-asserted-by":"publisher","first-page":"204062071989989","DOI":"10.1177\/2040620719899897","volume":"11","author":"T Jain","year":"2020","unstructured":"Jain, T. & Litzow, M. R. Management of toxicities associated with novel immunotherapy agents in acute lymphoblastic leukemia. Ther. Adv. Hematol. 11, 2040620719899897 (2020).","journal-title":"Ther. Adv. Hematol."},{"key":"68833_CR47","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/hon.2595","volume":"37","author":"SS Neelapu","year":"2019","unstructured":"Neelapu, S. S. Managing the toxicities of CAR T-cell therapy. Hematol. Oncol. 37, 48\u201352 (2019).","journal-title":"Hematol. Oncol."},{"key":"68833_CR48","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.yrtph.2017.09.001","volume":"90","author":"H Saber","year":"2017","unstructured":"Saber, H., Valle, P. D., Ricks, T. K. & Leighton, J. K. An FDA oncology analysis of CD3 bispecific constructs and first-in-human dose selection. Regul. Toxicol. Pharm. 90, 144\u2013152 (2017).","journal-title":"Regul. Toxicol. Pharm."},{"key":"68833_CR49","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1200\/JCO.21.01805","volume":"40","author":"RD Carvajal","year":"2022","unstructured":"Carvajal, R. D. et al. Phase I study of safety, tolerability, and efficacy of tebentafusp using a step-up dosing regimen and expansion in patients with metastatic uveal melanoma. J. Clin. Oncol. 40, 1939\u20131948 (2022).","journal-title":"J. Clin. Oncol."},{"key":"68833_CR50","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1200\/JCO.2010.32.7270","volume":"29","author":"MS Topp","year":"2011","unstructured":"Topp, M. S. et al. Targeted therapy with the T-Cell\u2013engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J. Clin. Oncol. 29, 2493\u20132498 (2011).","journal-title":"J. Clin. Oncol."},{"key":"68833_CR51","doi-asserted-by":"publisher","first-page":"100339","DOI":"10.1016\/j.jve.2023.100339","volume":"9","author":"H Patel","year":"2023","unstructured":"Patel, H. & Dub\u00e9, K. To prescreen or not to prescreen for broadly neutralizing antibody sensitivity in HIV cure-related trials. J. Virus Erad. 9, 100339 (2023).","journal-title":"J. Virus Erad."},{"key":"68833_CR52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007619","volume":"15","author":"M Pardons","year":"2019","unstructured":"Pardons, M. et al. Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection. PLoS Pathog. 15, e1007619 (2019).","journal-title":"PLoS Pathog."},{"key":"68833_CR53","first-page":"343","volume":"30","author":"JZ Li","year":"2016","unstructured":"Li, J. Z. et al. The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption. AIDS 30, 343\u2013353 (2016).","journal-title":"AIDS"},{"key":"68833_CR54","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.134196","volume":"5","author":"AO Pasternak","year":"2020","unstructured":"Pasternak, A. O. et al. Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART. JCI Insight 5, e134196 (2020).","journal-title":"JCI Insight"},{"key":"68833_CR55","doi-asserted-by":"publisher","unstructured":"Scheerder, M.-A. D. et al. In-depth analysis of the HIV reservoir confirms effectiveness and safety of dolutegravir\/lamivudine in a phase 4 randomized controlled switch trial (RUMBA). J. Infect. Dis. https:\/\/doi.org\/10.1093\/infdis\/jiae405 (2024).","DOI":"10.1093\/infdis\/jiae405"},{"key":"68833_CR56","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01605-22","volume":"96","author":"HA Martin","year":"2022","unstructured":"Martin, H. A. et al. New assay reveals vast excess of defective over intact HIV-1 transcripts in antiretroviral therapy-suppressed individuals. J. Virol. 96, e01605-22 (2022).","journal-title":"J. Virol."},{"key":"68833_CR57","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1016\/j.chom.2023.08.006","volume":"31","author":"M Dub\u00e9","year":"2023","unstructured":"Dub\u00e9, M. et al. Spontaneous HIV expression during suppressive ART is associated with the magnitude and function of HIV-specific CD4+ and CD8+ T cells. Cell Host Microbe 31, 1507\u20131522.e5 (2023).","journal-title":"Cell Host Microbe"},{"key":"68833_CR58","doi-asserted-by":"publisher","first-page":"3704","DOI":"10.1073\/pnas.1917876117","volume":"117","author":"H Imamichi","year":"2020","unstructured":"Imamichi, H. et al. Defective HIV-1 proviruses produce viral proteins. Proc. Natl. Acad. Sci. USA 117, 3704\u20133710 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"68833_CR59","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.chom.2017.03.008","volume":"21","author":"RA Pollack","year":"2017","unstructured":"Pollack, R. A. et al. Defective HIV-1 proviruses are expressed and can be recognized by cytotoxic T lymphocytes, which shape the proviral landscape. Cell Host Microbe 21, 494\u2013506.e4 (2017).","journal-title":"Cell Host Microbe"},{"key":"68833_CR60","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1158\/2159-8290.CD-17-0698","volume":"7","author":"J Gust","year":"2017","unstructured":"Gust, J. et al. Endothelial activation and blood\u2013brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov 7, 1404\u20131419 (2017).","journal-title":"Cancer Discov"},{"key":"68833_CR61","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.chom.2017.12.004","volume":"23","author":"Y Kim","year":"2018","unstructured":"Kim, Y., Anderson, J. L. & Lewin, S. R. Getting the \u201cKill\u201d into \u201cShock and Kill\u201d: strategies to eliminate latent HIV. Cell Host Microbe 23, 14\u201326 (2018).","journal-title":"Cell Host Microbe"},{"key":"68833_CR62","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev.genom.9.081307.164258","volume":"9","author":"MC Campbell","year":"2008","unstructured":"Campbell, M. C. & Tishkoff, S. A. African genetic diversity: implications for human demographic history, modern human origins, and complex disease mapping. Annu. Rev. Genom. Hum. Genet. 9, 403\u2013433 (2008).","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"68833_CR63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2318003121","volume":"121","author":"RL Paterson","year":"2024","unstructured":"Paterson, R. L. et al. An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 121, e2318003121 (2024).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"68833_CR64","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-75140-7","volume":"14","author":"V Karuppiah","year":"2024","unstructured":"Karuppiah, V. et al. Broadening alloselectivity of T cell receptors by structure guided engineering. Sci. Rep. 14, 26851 (2024).","journal-title":"Sci. Rep."},{"key":"68833_CR65","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54378-9","volume":"15","author":"G Murugesan","year":"2024","unstructured":"Murugesan, G. et al. Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen. Nat. Commun. 15, 10126 (2024).","journal-title":"Nat. Commun."},{"key":"68833_CR66","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32811-1","volume":"13","author":"A Poole","year":"2022","unstructured":"Poole, A. et al. Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen. Nat. Commun. 13, 5333 (2022).","journal-title":"Nat. Commun."},{"key":"68833_CR67","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.jim.2013.03.001","volume":"391","author":"H Yang","year":"2013","unstructured":"Yang, H. et al. Improved quantification of HIV-1-infected CD4+ T cells using an optimised method of intracellular HIV-1 gag p24 antigen detection. J. Immunol. Methods 391, 174\u2013178 (2013).","journal-title":"J. Immunol. Methods"},{"key":"68833_CR68","doi-asserted-by":"publisher","first-page":"197ra103","DOI":"10.1126\/scitranslmed.3006034","volume":"5","author":"BJ Cameron","year":"2013","unstructured":"Cameron, B. J. et al. Identification of a titin-derived HLA-A1\u2013presented peptide as a cross-reactive target for engineered MAGE A3\u2013directed T cells. Sci. Transl. Med. 5, 197ra103\u2013197ra103 (2013).","journal-title":"Sci. Transl. Med."},{"key":"68833_CR69","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1111\/bcp.13550","volume":"84","author":"J Gerven","year":"2018","unstructured":"Gerven, J. & Bonelli, M. Commentary on the EMA Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products. Br. J. Clin. Pharmacol. 84, 1401\u20131409 (2018).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"68833_CR70","unstructured":"European Medicines Agency. Guideline on Strategies to Identify and Mitigate Risks for First-in-Human and Early Clinical Trials with Investigational Medicinal Products. https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-strategies-identify-mitigate-risks-first-human-early-clinical-trials-investigational_en.pdf (2017)."},{"key":"68833_CR71","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.cct.2017.04.006","volume":"58","author":"W Guo","year":"2017","unstructured":"Guo, W., Wang, S.-J., Yang, S., Lynn, H. & Ji, Y. A Bayesian interval dose-finding design addressing Ockham\u2019s razor: mTPI-2. Contemp. Clin. Trials 58, 23\u201333 (2017).","journal-title":"Contemp. Clin. Trials"},{"key":"68833_CR72","doi-asserted-by":"publisher","unstructured":"G\u00e9raud, A. et al. Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review. Eur. J. Cancer https:\/\/doi.org\/10.1016\/j.ejca.2024.114075 (2024).","DOI":"10.1016\/j.ejca.2024.114075"},{"key":"68833_CR73","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","volume":"155","author":"Y-C Ho","year":"2013","unstructured":"Ho, Y.-C. et al. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155, 540\u2013551 (2013).","journal-title":"Cell"},{"key":"68833_CR74","doi-asserted-by":"publisher","first-page":"e1492","DOI":"10.21769\/BioProtoc.1492","volume":"5","author":"M Massanella","year":"2015","unstructured":"Massanella, M., Gianella, S., Lada, S., Richman, D. & Strain, M. Quantification of total and 2-LTR (long terminal repeat) HIV DNA, HIV RNA and herpesvirus DNA in PBMCs. BIO-Protoc. 5, e1492 (2015).","journal-title":"BIO-Protoc."},{"key":"68833_CR75","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103615","volume":"25","author":"NAJ Cassidy","year":"2022","unstructured":"Cassidy, N. A. J. et al. HIV reservoir quantification using cross-subtype multiplex ddPCR. iScience 25, 103615 (2022).","journal-title":"iScience"},{"key":"68833_CR76","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41586-022-04797-9","volume":"606","author":"MC Sneller","year":"2022","unstructured":"Sneller, M. C. et al. Combination anti-HIV antibodies provide sustained virological suppression. Nature 606, 375\u2013381 (2022).","journal-title":"Nature"},{"key":"68833_CR77","doi-asserted-by":"publisher","first-page":"e1005142","DOI":"10.1371\/journal.ppat.1005142","volume":"11","author":"OS S\u00f8gaard","year":"2015","unstructured":"S\u00f8gaard, O. S. et al. The depsipeptide romidepsin reverses HIV-1 latency in vivo. PLoS Pathog 11, e1005142 (2015).","journal-title":"PLoS Pathog"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68833-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68833-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68833-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T13:02:03Z","timestamp":1772715723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68833-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,31]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["68833"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-68833-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,31]]},"assertion":[{"value":"13 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"L.V. receives research grants from J&J, ViiV Healthcare and Gilead Sciences. J.N. has received fees for educational activities and\/or consultancies and\/or financial support for attending conferences from AbbVie, Gilead Sciences, Janssen-Cilag, Merck Sharp & Dohme and ViiV Healthcare; S.D.A has received research grants and\/or consulting fees from Gilead Sciences, GSK, MSD and ViiV Healthcare. A.J.U. has received financial support for attending a conference from Gilead Sciences. M.B. has received research grants and\/or consulting fees from ViiV, Gilead, MSD, GSK, Novavax, Valneva, Cipla, Mylan, Janssen, and Roche. V.E. has received fees for educational activities and\/or consultancies and\/or financial support for attending conferences from Gilead Sciences, Janssen-Cilag, Merck Sharp and Dohme and ViiV Healthcare. B.M. has received consultancy fees from AELIX Therapeutics SL and AbbVie and speaker fees from Gilead, Janssen and ViiV Healthcare. M.D. was supported by the NIH MDC grant RID-HIV: UM1AI164561 and PO1 AI178376. A.B., H.R., A.T., J.C., R.H., M.H., Y.Y., J.W., S.M., A.D.W., Z.W., P.K.S., K.T., and L.D. were\/are employees of Immunocore Ltd. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2207"}}