{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T12:14:49Z","timestamp":1792844089630,"version":"4.5.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Author is an employee of Janssen Research and Development.","id":[{"id":"https:\/\/ror.org\/05wae1a98","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Blood Cancer J."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Redirecting T cells to specifically kill malignant cells has been validated as an effective anti-cancer strategy in the clinic with the approval of blinatumomab for acute lymphoblastic leukemia. However, the immunosuppressive nature of the tumor microenvironment potentially poses a significant hurdle to T cell therapies. In hematological malignancies, the bone marrow (BM) niche is protective to leukemic stem cells and has minimized the efficacy of several anti-cancer drugs. In this study, we investigated the impact of the BM microenvironment on T cell redirection. Using bispecific antibodies targeting specific tumor antigens (CD123 and BCMA) and CD3, we observed that co-culture of acute myeloid leukemia or multiple myeloma cells with BM stromal cells protected tumor cells from bispecific antibody-T cell-mediated lysis in vitro and in vivo. Impaired CD3 redirection cytotoxicity was correlated with reduced T cell effector responses and cell\u2013cell contact with stromal cells was implicated in reducing T cell activation and conferring protection of cancer cells. Finally, blocking the VLA4 adhesion pathway in combination with CD3 redirection reduced the stromal-mediated inhibition of cytotoxicity and T cell activation. Our results lend support to inhibiting VLA4 interactions along with administering CD3 redirection therapeutics as a novel combinatorial regimen for robust anti-cancer responses.<\/jats:p>","DOI":"10.1038\/s41408-020-0331-4","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T09:04:26Z","timestamp":1591002266000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Blockade of VLA4 sensitizes leukemic and myeloma tumor cells to CD3 redirection in the bone marrow microenvironment"],"prefix":"10.1038","volume":"10","author":[{"given":"Priyanka","family":"Nair-Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen I.","family":"Rudnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopoldo","family":"Luistro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"McDaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhe","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodandaram","family":"Pillarisetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelin","family":"Joseph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Heidrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Packman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6942-8019","authenticated-orcid":false,"given":"Ricardo","family":"Attar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Gaudet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,1]]},"reference":[{"key":"331_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1182\/asheducation.V2012.1.35.3797926","volume":"2012","author":"E Paietta","year":"2012","unstructured":"Paietta, E. Minimal residual disease in acute myeloid leukemia: coming of age. Hematol. Am. Soc. Hematol. Educ. Program 2012, 35\u201342 (2012).","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"331_CR2","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.1182\/blood-2009-03-201053","volume":"114","author":"JL Harousseau","year":"2009","unstructured":"Harousseau, J. L., Attal, M. & Avet-Loiseau, H. The role of complete response in multiple myeloma. Blood. 114, 3139\u20133146 (2009).","journal-title":"Blood."},{"key":"331_CR3","doi-asserted-by":"publisher","first-page":"181","DOI":"10.4137\/CMO.S8528","volume":"7","author":"F El Rassi","year":"2013","unstructured":"El Rassi, F. & Arellano, M. Update on optimal management of acute myeloid leukemia. Clin. Med. Insights Oncol. 7, 181\u2013197 (2013).","journal-title":"Clin. Med. Insights Oncol."},{"key":"331_CR4","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1182\/blood-2011-01-332320","volume":"118","author":"J Martinez-Lopez","year":"2011","unstructured":"Martinez-Lopez, J. et al. Long-term prognostic significance of response in multiple myeloma after stem cell transplantation. Blood. 118, 529\u2013534 (2011).","journal-title":"Blood."},{"key":"331_CR5","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ctrv.2016.11.005","volume":"52","author":"F Malard","year":"2017","unstructured":"Malard, F., Harousseau, J. L. & Mohty, M. Multiple myeloma treatment at relapse after autologous stem cell transplantation: a practical analysis. Cancer Treat. Rev. 52, 41\u201347 (2017).","journal-title":"Cancer Treat. Rev."},{"key":"331_CR6","first-page":"1","volume":"21","author":"S Blatter","year":"2015","unstructured":"Blatter, S. & Rottenberg, S. Minimal residual disease in cancer therapy\u2013Small things make all the difference. Drug Resist. Updat. Rev. Comment. Antimicrob. Anticancer Chemother. 21\u201322, 1\u201310 (2015).","journal-title":"Drug Resist. Updat. Rev. Comment. Antimicrob. Anticancer Chemother."},{"key":"331_CR7","doi-asserted-by":"publisher","first-page":"345","DOI":"10.2174\/138920109787847493","volume":"10","author":"GW Basak","year":"2009","unstructured":"Basak, G. W., Srivastava, A. S., Malhotra, R. & Carrier, E. Multiple myeloma bone marrow niche. Curr. Pharm. Biotechnol. 10, 345\u2013346 (2009).","journal-title":"Curr. Pharm. Biotechnol."},{"issue":"4","key":"331_CR8","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1007\/s00018-016-2306-y","volume":"74","author":"Abel S\u00e1nchez-Aguilera","year":"2016","unstructured":"Sanchez-Aguilera A., Mendez-Ferrer S. The hematopoietic stem-cell niche in health and leukemia. Cell. Mol. Life Sci. 74, 579\u2013590 (2016).","journal-title":"Cellular and Molecular Life Sciences"},{"key":"331_CR9","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1182\/blood-2009-01-202606","volume":"114","author":"SW Lane","year":"2009","unstructured":"Lane, S. W., Scadden, D. T. & Gilliland, D. G. The leukemic stem cell niche: current concepts and therapeutic opportunities. Blood. 114, 1150\u20131157 (2009).","journal-title":"Blood."},{"key":"331_CR10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nri3132","volume":"12","author":"FE Mercier","year":"2011","unstructured":"Mercier, F. E., Ragu, C. & Scadden, D. T. The bone marrow at the crossroads of blood and immunity. Nat. Rev. Immunol. 12, 49\u201360 (2011).","journal-title":"Nat. Rev. Immunol."},{"key":"331_CR11","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/onc.2008.385","volume":"28","author":"K Noborio-Hatano","year":"2009","unstructured":"Noborio-Hatano, K. et al. Bortezomib overcomes cell-adhesion-mediated drug resistance through downregulation of VLA-4 expression in multiple myeloma. Oncogene. 28, 231\u2013242 (2009).","journal-title":"Oncogene."},{"key":"331_CR12","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500221","volume":"1","author":"AS Green","year":"2015","unstructured":"Green, A. S. et al. Pim kinases modulate resistance to FLT3 tyrosine kinase inhibitors in FLT3-ITD acute myeloid leukemia. Sci. Adv. 1, e1500221 (2015).","journal-title":"Sci. Adv."},{"key":"331_CR13","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.3324\/haematol.2014.113852","volume":"100","author":"DS Krause","year":"2015","unstructured":"Krause, D. S. & Scadden, D. T. A hostel for the hostile: the bone marrow niche in hematologic neoplasms. Haematologica. 100, 1376\u20131387 (2015).","journal-title":"Haematologica."},{"key":"331_CR14","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.cell.2013.12.041","volume":"156","author":"CP Pallasch","year":"2014","unstructured":"Pallasch, C. P. et al. Sensitizing protective tumor microenvironments to antibody-mediated therapy. Cell 156, 590\u2013602 (2014).","journal-title":"Cell"},{"key":"331_CR15","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.coi.2016.02.006","volume":"40","author":"EA Zhukovsky","year":"2016","unstructured":"Zhukovsky, E. A., Morse, R. J. & Maus, M. V. Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection. Curr. Opin. Immunol. 40, 24\u201335 (2016).","journal-title":"Curr. Opin. Immunol."},{"key":"331_CR16","doi-asserted-by":"publisher","first-page":"4134","DOI":"10.1200\/JCO.2014.56.3247","volume":"32","author":"MS Topp","year":"2014","unstructured":"Topp, M. S. et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J. Clin. Oncol. 32, 4134\u20134140 (2014).","journal-title":"J. Clin. Oncol."},{"key":"331_CR17","doi-asserted-by":"publisher","first-page":"5145","DOI":"10.1073\/pnas.1220145110","volume":"110","author":"AF Labrijn","year":"2013","unstructured":"Labrijn, A. F. et al. Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proc. Natl Acad. Sci. USA 110, 5145\u20135150 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"331_CR18","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1038\/nprot.2014.169","volume":"9","author":"AF Labrijn","year":"2014","unstructured":"Labrijn, A. F. et al. Controlled Fab-arm exchange for the generation of stable bispecific IgG1. Nat. Protoc. 9, 2450\u20132463 (2014).","journal-title":"Nat. Protoc."},{"key":"331_CR19","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1007\/s11899-015-0255-4","volume":"10","author":"A Rashidi","year":"2015","unstructured":"Rashidi, A. & Uy, G. L. Targeting the microenvironment in acute myeloid leukemia. Curr. Hematol. Malig. Rep. 10, 126\u201331. (2015).","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"331_CR20","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/leu.2008.48","volume":"22","author":"Y Shiozawa","year":"2008","unstructured":"Shiozawa, Y., Havens, A. M., Pienta, K. J. & Taichman, R. S. The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites. Leukemia 22, 941\u2013950 (2008).","journal-title":"Leukemia"},{"key":"331_CR21","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1038\/nrclinonc.2011.31","volume":"8","author":"C Tripodo","year":"2011","unstructured":"Tripodo, C. et al. The bone marrow stroma in hematological neoplasms\u2013a guilty bystander. Nat. Rev. Clin. Oncol. 8, 456\u2013466 (2011).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"331_CR22","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1158\/1078-0432.CCR-07-2223","volume":"14","author":"MB Meads","year":"2008","unstructured":"Meads, M. B., Hazlehurst, L. A. & Dalton, W. S. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin. Cancer Res. 14, 2519\u20132526 (2008).","journal-title":"Clin. Cancer Res."},{"key":"331_CR23","doi-asserted-by":"publisher","first-page":"6682","DOI":"10.4049\/jimmunol.0900080","volume":"182","author":"S Chikuma","year":"2009","unstructured":"Chikuma, S. et al. PD-1-mediated suppression of IL-2 production induces CD8+ T cell anergy in vivo. J. Immunol. 182, 6682\u20136689 (2009).","journal-title":"J. Immunol."},{"key":"331_CR24","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1097\/CJI.0b013e3181fad2b0","volume":"33","author":"T Inozume","year":"2010","unstructured":"Inozume, T. et al. Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells. J. Immunother. 33, 956\u201364. (2010).","journal-title":"J. Immunother."},{"key":"331_CR25","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1172\/JCI73639","volume":"124","author":"A Gros","year":"2014","unstructured":"Gros, A. et al. PD-1 identifies the patient-specific CD8(+) tumor-reactive repertoire infiltrating human tumors. J. Clin. Invest. 124, 2246\u20132259 (2014).","journal-title":"J. Clin. Invest."},{"key":"331_CR26","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1104448","volume":"5","author":"S Simon","year":"2016","unstructured":"Simon, S. et al. PD-1 expression conditions T cell avidity within an antigen-specific repertoire. Oncoimmunology 5, e1104448 (2016).","journal-title":"Oncoimmunology"},{"key":"331_CR27","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/nm.4051","volume":"22","author":"A Gros","year":"2016","unstructured":"Gros, A. et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat. Med. 22, 433\u2013438 (2016).","journal-title":"Nat. Med."},{"key":"331_CR28","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/BF00241263","volume":"39","author":"B Huard","year":"1994","unstructured":"Huard, B., Gaulard, P., Faure, F., Hercend, T. & Triebel, F. Cellular expression and tissue distribution of the human LAG-3-encoded protein, an MHC class II ligand. Immunogenetics 39, 213\u2013217 (1994).","journal-title":"Immunogenetics"},{"key":"331_CR29","doi-asserted-by":"publisher","first-page":"2492","DOI":"10.1002\/eji.200939274","volume":"39","author":"WD Hastings","year":"2009","unstructured":"Hastings, W. D. et al. TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. Eur. J. Immunol. 39, 2492\u20132501 (2009).","journal-title":"Eur. J. Immunol."},{"key":"331_CR30","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1038\/nm909","volume":"9","author":"T Matsunaga","year":"2003","unstructured":"Matsunaga, T. et al. Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia. Nat. Med. 9, 1158\u20131165 (2003).","journal-title":"Nat. Med."},{"key":"331_CR31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/bs.acr.2017.11.001","volume":"137","author":"S Maji","year":"2018","unstructured":"Maji, S. et al. Bcl-2 antiapoptotic family proteins and chemoresistance in cancer. Adv. Cancer Res. 137, 37\u201375 (2018).","journal-title":"Adv. Cancer Res."},{"key":"331_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0141669","volume":"10","author":"W Deisting","year":"2015","unstructured":"Deisting, W., Raum, T., Kufer, P., Baeuerle, P. A. & Munz, M. Impact of diverse immune evasion mechanisms of cancer cells on T cells engaged by EpCAM\/CD3-bispecific antibody construct AMG 110. PLoS ONE 10, e0141669 (2015).","journal-title":"PLoS ONE"},{"key":"331_CR33","doi-asserted-by":"publisher","first-page":"2589","DOI":"10.18632\/oncotarget.2661","volume":"6","author":"L Raffaghello","year":"2015","unstructured":"Raffaghello, L., Vacca, A., Pistoia, V. & Ribatti, D. Cancer associated fibroblasts in hematological malignancies. Oncotarget 6, 2589\u20132603 (2015).","journal-title":"Oncotarget"},{"key":"331_CR34","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1177\/2040620715619307","volume":"7","author":"A Rashidi","year":"2016","unstructured":"Rashidi, A. & DiPersio, J. F. Targeting the leukemia-stroma interaction in acute myeloid leukemia: rationale and latest evidence. Ther. Adv. Hematol. 7, 40\u201351 (2016).","journal-title":"Ther. Adv. Hematol."},{"key":"331_CR35","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.4049\/jimmunol.155.6.2938","volume":"155","author":"T Sato","year":"1995","unstructured":"Sato, T., Tachibana, K., Nojima, Y., D\u2019Avirro, N. & Morimoto, C. Role of the VLA-4 molecule in T cell costimulation. Identification of the tyrosine phosphorylation pattern induced by the ligation of VLA-4. J. Immunol. 155, 2938\u20132947 (1995).","journal-title":"J. Immunol."},{"key":"331_CR36","doi-asserted-by":"crossref","first-page":"785","DOI":"10.4049\/jimmunol.145.3.785","volume":"145","author":"LS Davis","year":"1990","unstructured":"Davis, L. S., Oppenheimer-Marks, N., Bednarczyk, J. L., McIntyre, B. W. & Lipsky, P. E. Fibronectin promotes proliferation of naive and memory T cells by signaling through both the VLA-4 and VLA-5 integrin molecules. J. Immunol. 145, 785\u2013793 (1990).","journal-title":"J. Immunol."},{"key":"331_CR37","doi-asserted-by":"crossref","first-page":"59","DOI":"10.4049\/jimmunol.145.1.59","volume":"145","author":"Y Shimizu","year":"1990","unstructured":"Shimizu, Y., van Seventer, G. A., Horgan, K. J. & Shaw, S. Costimulation of proliferative responses of resting CD4+ T cells by the interaction of VLA-4 and VLA-5 with fibronectin or VLA-6 with laminin. J. Immunol. 145, 59\u201367 (1990).","journal-title":"J. Immunol."},{"key":"331_CR38","doi-asserted-by":"publisher","first-page":"11058","DOI":"10.1073\/pnas.0307927101","volume":"101","author":"M Mittelbrunn","year":"2004","unstructured":"Mittelbrunn, M. et al. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses. Proc. Natl Acad. Sci. USA 101, 11058\u201311063 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"331_CR39","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1111\/ane.12080","volume":"128","author":"S Marousi","year":"2013","unstructured":"Marousi, S. et al. Immune cells after prolonged Natalizumab therapy: implications for effectiveness and safety. Acta Neurol. Scand. 128, e1\u2013e5 (2013).","journal-title":"Acta Neurol. Scand."},{"key":"331_CR40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047578","volume":"7","author":"L Bornsen","year":"2012","unstructured":"Bornsen, L. et al. Effect of natalizumab on circulating CD4+ T-cells in multiple sclerosis. PLoS ONE 7, e47578 (2012).","journal-title":"PLoS ONE"},{"key":"331_CR41","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1212\/WNL.0b013e3181a8266f","volume":"72","author":"P Kivisakk","year":"2009","unstructured":"Kivisakk, P. et al. Natalizumab treatment is associated with peripheral sequestration of proinflammatory T cells. Neurology 72, 1922\u20131930 (2009).","journal-title":"Neurology"},{"key":"331_CR42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052208","volume":"7","author":"TF Benkert","year":"2012","unstructured":"Benkert, T. F. et al. Natalizumab exerts direct signaling capacity and supports a pro-inflammatory phenotype in some patients with multiple sclerosis. PLoS ONE 7, e52208 (2012).","journal-title":"PLoS ONE"},{"key":"331_CR43","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000210","volume":"3","author":"K Kimura","year":"2016","unstructured":"Kimura, K. et al. Disrupted balance of T cells under natalizumab treatment in multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 3, e210 (2016).","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"331_CR44","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s13045-017-0522-z","volume":"10","author":"S Yu","year":"2017","unstructured":"Yu, S. et al. Recent advances of bispecific antibodies in solid tumors. J. Hematol. Oncol. 10, 155 (2017).","journal-title":"J. Hematol. Oncol."},{"key":"331_CR45","unstructured":"Ishiguro T. et al. An anti-glypican 3\/CD3 bispecific T cell-redirecting antibody for treatment of solid tumors. Sci. Transl. Med. 9, 4291 (2017)."},{"key":"331_CR46","doi-asserted-by":"publisher","first-page":"20212","DOI":"10.1073\/pnas.1320318110","volume":"110","author":"C Feig","year":"2013","unstructured":"Feig, C. et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer. Proc. Natl Acad. Sci. USA 110, 20212\u201320217 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"}],"container-title":["Blood Cancer Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41408-020-0331-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-020-0331-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41408-020-0331-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T15:52:29Z","timestamp":1696175549000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41408-020-0331-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["331"],"URL":"https:\/\/doi.org\/10.1038\/s41408-020-0331-4","relation":{},"ISSN":["2044-5385"],"issn-type":[{"value":"2044-5385","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]},"assertion":[{"value":"28 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors are employees of Janssen Research and Development, LLC.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"65"}}