{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:46:57Z","timestamp":1760143617843,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Associazione Italiana Ricerca contro il Cancro (AIRC)","award":["IG19036","21147","ANR-10-LABX-53"],"award-info":[{"award-number":["IG19036","21147","ANR-10-LABX-53"]}]},{"name":"French National Research Agency","award":["IG19036","21147","ANR-10-LABX-53"],"award-info":[{"award-number":["IG19036","21147","ANR-10-LABX-53"]}]},{"name":"Associazione Italiana contro le Leucemie, Linfomi e Mieloma (AIL)","award":["IG19036","21147","ANR-10-LABX-53"],"award-info":[{"award-number":["IG19036","21147","ANR-10-LABX-53"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>We designed, produced, and purified a novel IgG1-like, bispecific antibody (bsAb) directed against B-cell maturation antigen (BCMA), expressed by multiple myeloma (MM) cells, and an immune checkpoint inhibitor (ICI), PDL1, expressed in the MM microenvironment. The BCMA\u00d7PDL1 bsAb was fully characterized in vitro. BCMA\u00d7PDL1 bound specifically and simultaneously, with nM affinity, to both native membrane-bound antigens and to the recombinant soluble antigen fragments, as shown by immunophenotyping analyses and surface plasmon resonance (SPR), respectively. The binding affinity of bsAb for PDL1 and BCMA was similar to each other, but PDL1 affinity was about 10-fold lower in the bsAb compared to parent mAb, probably due to the steric hindrance associated with the more internal anti-PDL1 Fab. The bsAb was also able to functionally block both antigen targets with IC50 in the nM range. The bsAb Fc was functional, inducing human-complement-dependent cytotoxicity as well as ADCC by NK cells in 24 h killing assays. Finally, BCMA\u00d7PDL1 was effective in 7-day killing assays with peripheral blood mononuclear cells as effectors, inducing up to 75% of target MM cell line killing at a physiologically attainable, 6 nM, concentration. These data provide the necessary basis for future optimization and in vivo testing of this novel bsAb.<\/jats:p>","DOI":"10.3390\/antib13010015","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T11:50:07Z","timestamp":1708429807000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Bispecific IgG1 Antibody Targeting BCMA and PDL1"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5094-7150","authenticated-orcid":false,"given":"Irene","family":"Cattaneo","sequence":"first","affiliation":[{"name":"Division of Hematology, Center of Cellular Therapy \u201cG. Lanzani\u201d, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, 24122 Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvie","family":"Choblet","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique UAR3426 \u201cBaculovirus et Therapie\u201d, 30380 Saint-Christol-Lez-Al\u00e8s, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rut","family":"Valgardsdottir","sequence":"additional","affiliation":[{"name":"Division of Hematology, Center of Cellular Therapy \u201cG. Lanzani\u201d, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, 24122 Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0165-595X","authenticated-orcid":false,"given":"Muriel","family":"Roth","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique UAR3426 \u201cBaculovirus et Therapie\u201d, 30380 Saint-Christol-Lez-Al\u00e8s, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annamaria","family":"Massafra","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacodynamics and Pharmacokinetics, Department of Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri\u2014IRCCS, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-6704","authenticated-orcid":false,"given":"Marten","family":"Beeg","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacodynamics and Pharmacokinetics, Department of Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri\u2014IRCCS, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1014-6225","authenticated-orcid":false,"given":"Marco","family":"Gobbi","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacodynamics and Pharmacokinetics, Department of Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri\u2014IRCCS, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Duonor-Cerutti","sequence":"additional","affiliation":[{"name":"Centre National de la Recherche Scientifique UAR3426 \u201cBaculovirus et Therapie\u201d, 30380 Saint-Christol-Lez-Al\u00e8s, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-909X","authenticated-orcid":false,"given":"Jos\u00e9e","family":"Golay","sequence":"additional","affiliation":[{"name":"Division of Hematology, Center of Cellular Therapy \u201cG. Lanzani\u201d, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, 24122 Bergamo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jaut.2017.06.002","article-title":"Direct Targeting of Cancer Cells with Antibodies: What Can We Learn from the Successes and Failure of Unconjugated Antibodies for Lymphoid Neoplasias?","volume":"85","author":"Golay","year":"2017","journal-title":"J. Autoimmun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1097\/CCO.0000000000000966","article-title":"Update on Bi-Specific Monoclonal Antibodies for Blood Cancers","volume":"35","author":"Shouse","year":"2023","journal-title":"Curr. Opin. 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