{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:45:20Z","timestamp":1793065520534,"version":"4.5.0"},"posted":{"date-parts":[[2026,4,10]]},"group-title":"Immunology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01AI136758"],"award-info":[{"award-number":["R01AI136758"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["1S10RR13878"],"award-info":[{"award-number":["1S10RR13878"]}]},{"name":"NIH","award":["1S10RR026659"],"award-info":[{"award-number":["1S10RR026659"]}]},{"award":["MRI:DBI-1532078"],"award-info":[{"award-number":["MRI:DBI-1532078"]}],"id":[{"id":"https:\/\/ror.org\/02hxgd925","id-type":"ROR","asserted-by":"publisher"}]},{"award":["MRI:CHE-2018388"],"award-info":[{"award-number":["MRI:CHE-2018388"]}],"id":[{"id":"https:\/\/ror.org\/02hxgd925","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2015066:MNL"],"award-info":[{"award-number":["2015066:MNL"]}],"id":[{"id":"https:\/\/ror.org\/02hxgd925","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>In the course of testing mAb-based therapies to eradicate the persistent reservoir of HIV infection, we investigated the efficacy and mode of killing of HIV-infected cells by two categories of cytotoxic immunoconjugates (CICs) targeted by the same mAb, an immunotoxin (IT) and antibody-drug conjugate (ADC).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We performed metabolic and transcriptional analyses of treatment effects on the persistently-infected cell line H9\/NL4-3. Cells were treated with CIC\u2019s consisting of the anti-gp41 mAb 7B2 conjugated to either deglycosylated ricin A chain (dgA) or to the highly cytotoxic anthracycline derivative PNU-159682. At intervals up to 24 hr, intracellular metabolites were quantified by\n                    <jats:sup>1<\/jats:sup>\n                    H nuclear magnetic resonance spectroscopy, and the transcriptome analyzed by RNA-Seq.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Six hr post treatment, 7B2-dgA elicited both metabolic and transcriptional alterations, whereas 7B2-PNU treated cells did not differ from untreated cells. 7B2-dgA treated cells exhibited elevated intracellular levels of many amino acids, and activation of gene pathways for apoptosis, intracellular signaling, and immune activation. By 24 hr, both 7B2-dgA and 7B2-PNU treated cells differed markedly from untreated. Many of the changes observed following 7B2-PNU treatment at 24 hr were similar to those observed at 6hr following 7B2-dgA, likely indicating processes involved in cell death, but a number of alterations were unique to either IT or ADC treated cells.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>An IT and ADC showed both similarities and differences in their cytotoxic effects. These results raise the question of whether the mode of cell killing could be a determinant of clinical efficacy. Although these studies were aimed at targeting the persistent reservoir of HIV infection, they have relevance for the design of CICs to treat cancer and other conditions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>SUMMARY<\/jats:title>\n                  <jats:p>The use of cytotoxic immunoconjugates, wherein an antibody is attached to a cellular poison, is effective in the treatment of cancer and other conditions. We seek to extend these results to treating HIV and other chronic viral infections. We analyzed the molecular mechanisms of cell killing when the same antibody was attached to different toxic structures. We report that each immunoconjugate induced both common and distinct patterns of killing. Such differences may have clinical relevance.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.07.717054","type":"posted-content","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:15:19Z","timestamp":1775855719000},"source":"Crossref","is-referenced-by-count":1,"title":["Anti-HIV Immunotoxin and Antibody-Drug Conjugate Display Both Common and Distinct Effects in Killing Target Cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1622-4386","authenticated-orcid":false,"given":"Seth H.","family":"Pincus","sequence":"first","affiliation":[{"name":"Dept of Chemistry & Biochemistry, Montana State University, Bozeman MT USA 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tami","family":"Peters","sequence":"additional","affiliation":[{"name":"Dept of Chemistry & Biochemistry, Montana State University, Bozeman MT USA 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Stackhouse","sequence":"additional","affiliation":[{"name":"Dept of Chemistry & Biochemistry, Montana State University, Bozeman MT USA 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3499-6606","authenticated-orcid":false,"given":"Galen","family":"O\u2019Shea-Stone","sequence":"additional","affiliation":[{"name":"Dept of Chemistry & Biochemistry, Montana State University, Bozeman MT USA 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Cole","sequence":"additional","affiliation":[{"name":"Dept of Chemistry & Biochemistry, Montana State University, Bozeman MT USA 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8966-8714","authenticated-orcid":false,"given":"Brian","family":"Tripet","sequence":"additional","affiliation":[{"name":"Dept of Chemistry & Biochemistry, Montana State University, Bozeman MT USA 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2778-1463","authenticated-orcid":false,"given":"Val\u00e9rie","family":"Copi\u00e9","sequence":"additional","affiliation":[{"name":"Dept of Chemistry & Biochemistry, Montana State University, Bozeman MT USA 59717"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041313301552000_2026.04.07.717054v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00647-00624"},{"key":"2026041313301552000_2026.04.07.717054v1.2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01154-23"},{"key":"2026041313301552000_2026.04.07.717054v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines11040829"},{"key":"2026041313301552000_2026.04.07.717054v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01955-16"},{"key":"2026041313301552000_2026.04.07.717054v1.5","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01360-16"},{"key":"2026041313301552000_2026.04.07.717054v1.6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.2236"},{"key":"2026041313301552000_2026.04.07.717054v1.7","first-page":"1041","article-title":"In vitro effects of anti-HIV immunotoxins directed against multiple epitopes on the HIV-1 envelope glycoprotein gp160 AIDS","volume":"12","year":"1996","journal-title":"Res Hum Retrovirus"},{"key":"2026041313301552000_2026.04.07.717054v1.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.1.332"},{"key":"2026041313301552000_2026.04.07.717054v1.9","doi-asserted-by":"crossref","first-page":"4315","DOI":"10.4049\/jimmunol.146.12.4315","article-title":"In vitro efficacy of anti-HIV immunotoxins targeted by various antibodies to the envelope protein","volume":"146","year":"1991","journal-title":"J Immunol"},{"key":"2026041313301552000_2026.04.07.717054v1.10","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.4049\/jimmunol.142.9.3070","article-title":"Treatment of HIV tissue culture infection with monoclonal antibody-ricin A chain conjugates","volume":"142","year":"1989","journal-title":"J Immunol"},{"key":"2026041313301552000_2026.04.07.717054v1.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.6.1987"},{"key":"2026041313301552000_2026.04.07.717054v1.12","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1126\/science.2847316","article-title":"HIV-infected cells are killed by rCD4-ricin A chain","volume":"242","year":"1988","journal-title":"Science (New York, NY)"},{"key":"2026041313301552000_2026.04.07.717054v1.13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003872"},{"key":"2026041313301552000_2026.04.07.717054v1.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000803"},{"key":"2026041313301552000_2026.04.07.717054v1.15","doi-asserted-by":"publisher","DOI":"10.1086\/315351"},{"key":"2026041313301552000_2026.04.07.717054v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2026.109602"},{"key":"2026041313301552000_2026.04.07.717054v1.17","doi-asserted-by":"publisher","DOI":"10.3390\/antib15010012"},{"key":"2026041313301552000_2026.04.07.717054v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(02)00026-1"},{"key":"2026041313301552000_2026.04.07.717054v1.19","first-page":"1297","article-title":"Effect of immunosuppressive agents on the immunogenicity and efficacy of an immunotoxin in mice Clinical cancer research : an official","volume":"4","year":"1998","journal-title":"journal of the American Association for Cancer Research"},{"key":"2026041313301552000_2026.04.07.717054v1.20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701430"},{"key":"2026041313301552000_2026.04.07.717054v1.21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01261"},{"key":"2026041313301552000_2026.04.07.717054v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405153111"},{"key":"2026041313301552000_2026.04.07.717054v1.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321126111"},{"key":"2026041313301552000_2026.04.07.717054v1.24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1386190"},{"key":"2026041313301552000_2026.04.07.717054v1.25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005042"},{"key":"2026041313301552000_2026.04.07.717054v1.26","first-page":"223","article-title":"The GLP large scale preparation of immunotoxins containing deglycosylated ricin A chain and a hindered disulfide bond","volume":"1991","year":"1991","journal-title":"J Immunol Methods"},{"key":"2026041313301552000_2026.04.07.717054v1.27","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/aid.1995.11.533","article-title":"Expression and characterization of CD4-IgG2, a novel heterotetramer that neutralizes primary HIV-1 isolates AIDS","volume":"11","year":"1995","journal-title":"Res Hum Retroviruses"},{"key":"2026041313301552000_2026.04.07.717054v1.28","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.59.2.284-291.1986"},{"key":"2026041313301552000_2026.04.07.717054v1.29","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14120815"},{"key":"2026041313301552000_2026.04.07.717054v1.30","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.922"},{"key":"2026041313301552000_2026.04.07.717054v1.31","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.3.745"},{"key":"2026041313301552000_2026.04.07.717054v1.32","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9070774"},{"key":"2026041313301552000_2026.04.07.717054v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.70"},{"key":"2026041313301552000_2026.04.07.717054v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112186"},{"key":"2026041313301552000_2026.04.07.717054v1.35","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00617"},{"key":"2026041313301552000_2026.04.07.717054v1.36","doi-asserted-by":"publisher","DOI":"10.1097\/IN9.0000000000000014"},{"key":"2026041313301552000_2026.04.07.717054v1.37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.886822"},{"key":"2026041313301552000_2026.04.07.717054v1.38","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-20-0707"},{"key":"2026041313301552000_2026.04.07.717054v1.39","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16050984"},{"key":"2026041313301552000_2026.04.07.717054v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.10.056"},{"key":"2026041313301552000_2026.04.07.717054v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107906"},{"key":"2026041313301552000_2026.04.07.717054v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.268"},{"key":"2026041313301552000_2026.04.07.717054v1.43","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1162662"},{"key":"2026041313301552000_2026.04.07.717054v1.44","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27407"},{"key":"2026041313301552000_2026.04.07.717054v1.45","doi-asserted-by":"publisher","DOI":"10.1084\/jem.2.2.197"},{"key":"2026041313301552000_2026.04.07.717054v1.46","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.18.2342"},{"key":"2026041313301552000_2026.04.07.717054v1.47","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13060377"},{"key":"2026041313301552000_2026.04.07.717054v1.48","doi-asserted-by":"publisher","DOI":"10.3390\/toxins11060350"},{"key":"2026041313301552000_2026.04.07.717054v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2024.116890"},{"key":"2026041313301552000_2026.04.07.717054v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2024.04.007"},{"key":"2026041313301552000_2026.04.07.717054v1.51","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1845"},{"key":"2026041313301552000_2026.04.07.717054v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127640"},{"key":"2026041313301552000_2026.04.07.717054v1.53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0285161"},{"key":"2026041313301552000_2026.04.07.717054v1.54","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-1821"},{"key":"2026041313301552000_2026.04.07.717054v1.55","doi-asserted-by":"crossref","unstructured":"Tolcher, A. , Meric-Bernstam, F. , McKean, M. , Beerli, R. , Waldmeier, L. , Gebleux, R. , et al. (2021) NBE-002: A novel anthracycline-based antibody-drug conjugate (ADC) targeting ROR1 for the treatment of advanced solid tumors\u2014A phase 1\/2 clinical trial In J. Clin. Oncol., TPS1108","DOI":"10.1200\/JCO.2021.39.15_suppl.TPS1108"},{"key":"2026041313301552000_2026.04.07.717054v1.56","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-2035"},{"key":"2026041313301552000_2026.04.07.717054v1.57","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0464-1"},{"key":"2026041313301552000_2026.04.07.717054v1.58","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113480"},{"key":"2026041313301552000_2026.04.07.717054v1.59","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.6b00362"},{"key":"2026041313301552000_2026.04.07.717054v1.60","doi-asserted-by":"publisher","DOI":"10.1126\/science.adk1831"},{"key":"2026041313301552000_2026.04.07.717054v1.61","doi-asserted-by":"publisher","DOI":"10.3390\/v15122435"},{"key":"2026041313301552000_2026.04.07.717054v1.62","doi-asserted-by":"publisher","DOI":"10.3389\/FMICB.2022.862270"},{"key":"2026041313301552000_2026.04.07.717054v1.63","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-050520-112001"},{"key":"2026041313301552000_2026.04.07.717054v1.64","doi-asserted-by":"publisher","DOI":"10.1126\/science.adf7966"},{"key":"2026041313301552000_2026.04.07.717054v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02547-6"},{"key":"2026041313301552000_2026.04.07.717054v1.66","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02570-7"},{"key":"2026041313301552000_2026.04.07.717054v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09929-5"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.07.717054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T20:30:23Z","timestamp":1776112223000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.07.717054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":67,"URL":"https:\/\/doi.org\/10.64898\/2026.04.07.717054","relation":{},"subject":[],"published":{"date-parts":[[2026,4,10]]},"subtype":"preprint"}}