Publications

Programs

CD3 Bispecific Antibodies

CD28 Bispecific Antibodies

TL1A Programs

Plamotamab (CD20 x CD3 Bispecific Antibody)

Riedell, P.A., et al. 2024, American Society of Hematology (poster). Plamotamab: First Presentation of Subcutaneous Administration in a Phase 1 Dose-Escalation Study in Heavily Pretreated R/R NHL Patients Who Had Prior CAR-T Cell Therapy

Patel, K., et al. 2022, American Society of Hematology (poster). A Phase 1 Study of Plamotamab, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients With Relapsed/Refractory Non-Hodgkin’s Lymphoma: Recommended Dose Safety/Efficacy Update and Escalation Exposure-Response Analysis

Patel, K., et al. 2021, American Society of Hematology (poster). Phase 1 Safety and Anti-tumor Activity of Plamotamab (XmAb13676), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Subjects with Relapsed/Refractory Non-Hodgkin’s Lymphoma

Patel, K., et al. 2019, American Society of Hematology (poster). Preliminary Safety and Anti-Tumor Activity of XmAb13676, an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Non-Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia

Chu, S. Y., et al. 2014, Blood (poster) 124(21), 3111. Immunotherapy with long-lived anti-CD20 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human B cell lines and of circulating and lymphoid B cells in monkeys: a potential therapy for B cell lymphomas and leukemias.

XmAb®819 (ENPP3 x CD3 Bispecific Antibody)

Pal, S.K., et al. 2022, Society for Immunotherapy of Cancer (poster). A Phase 1, Multiple-Dose Study to Evaluate the Safety and Tolerability of XmAb819 in Patients With Relapsed or Refractory Clear Cell Renal Cell Carcinoma

Nisthal, A., et al. 2020, American Association for Cancer Research (poster). XmAb30819, an XmAb®2+1 ENPP3 x CD3 bispecific antibody for RCC, demonstrates safety and efficacy in in vivo preclinical studies

XmAb®541 (CLDN6 x CD3 Bispecific Antibody)

Faber, M.S., et al. 2021, American Association for Cancer Research (poster). Bispecific claudin-6 x CD3 antibodies in a 2+1 format demonstrate selectivity and activity on human ovarian cancer cells

Additional XmAb® 2+1 Bispecific Antibody Programs

Kelly, W.K., et al. 2023, Cancer Discov OF1–OF14 (paper). Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study

XmAb®808 (B7-H3 x CD28 Bispecific Antibody)

Bupathi, M., et al. 2023, Society for Immunotherapy of Cancer (poster). A phase 1, first-in-human, open-label, dose-finding and expansion study of XmAb808, a B7H3 x CD28 bispecific antibody, in combination with pembrolizumab in patients with advanced solid tumors

CD28 Bispecific Antibody Platform

Dragovic, M. A., et al. 2023, American Association for Cancer Research (poster). Tumor-specific CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors

Hedvat, M., et al. 2020, Society for Immunotherapy of Cancer (poster). Tumor-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors

XmAb®942 (Xtend anti-TL1A)

Hung, K. et al. 2025, ECCO (poster). Phase 1/2 Study to Assess Safety, Tolerability, and Efficacy of XmAb942 (anti-TL1A) in Healthy Participants and Participants With Ulcerative Colitis

Ernst, J., et al. 2024, UEG Week (poster). Discovery and Characterization of a Novel High-Affinity Anti-TL1A Monoclonal Antibody with Extended Half-Life for the Treatment of Inflammatory Bowel Disease

Fc Technology

Bispecific Fc Domain

Moore, G.L., Bautista, C., Pong, E., Nguyen, D.H., Jacinto, J., Eivazi, A., Muchhal, U.S., Karki, S., Chu, S.Y., and Lazar, G.A. 2011. A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens. mAbs 3(6): 546-557

Chu, S. Y., Lee, S., Rashid, R., Chen, H., Chan, E. W., Phung, S., Pong, E., Endo, N. A., Miranda, Y., Bonzon, C., Leung, I. W., Muchhal, U. S., Moore, G. L., Bernett, M. J., Szymkowski, D. E., and Desjarlais, J. R. 2014. Immunotherapy with long-lived anti-CD20 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human B cell lines and of circulating and lymphoid B cells in monkeys: a potential therapy for B cell lymphomas and leukemias. Blood 124(21), 3111

Bernett, M.J., Bonzon, C., Rashid, R., Varma, R., Avery, K.N, Leung. I.W.L., Chu. S.Y., Muchhal, U.S., Moore, G.L., and Desjarlais, J.R. 2017. IL15/IL15Rα heterodimeric Fc-fusions with extended half-lives. AACR Annual Meeting IL15/IL15Rα

Moore, G.L., Hedvat, M., Bernett, M.J., Varma, R., Schubbert, S., Bonzon, C., Avery, K.A., Rashid, R., Nisthal, A., Bogaert, L., Leung, I.W.L., Chu, S.Y., Muchhal, U.S., and Desjarlais, J.R. 2017. Combination of PD1 blockade and T cell costimulation by bispecific antibodies promotes human T cell activation and proliferation. AACR Annual Meeting (poster)

Nisthal, A., Bernett, M.J., Moore, G.L., Hedvat, M., Bonzon, C., Chu, S.Y., Rashid, R., Avery, K., Umesh, U.S. and Desjarlais, J.R. 2016. Mulitple bispesific combinations promote T cell activation. IBC’s Antibody Engineering & Therapeutics Conference (poster)

Moore, G.L., Bernett, M.J., Rashid, R., Pong, E.W., Nguyen, D.H., Jacinto, J., Eivazi, A., Nisthal, A., Diaz, J.E., Chu, S.Y., Muchhal, U.S. and Desjarlais, J.R. 2019. A robust heterodimeric Fc platform engineered for efficient development of bispecific antibodies of multiple formats. Methods. 154:38-50

Cytotoxic Fc Domain

Lazar, G.A., Dang, W., Karki, S., Vafa, O., Peng, J.S., Hyun, L., Chan, C., Chung, H.S., Eivazi, A., Yoder, S.C., Vielmetter, J., Carmichael, D.F., Hayes, R.J., and Dahiyat, B.I. 2006 Engineered antibody Fc variants with enhanced effector function. PNAS 103(11), 4005-4010

Horton, H.M., Bernett, M.J., Pong, E., Peipp, M., Karki, S., Chu, S.Y., Richards, J.O., Vostiar, I., Joyce, P.F., Repp, R., Desjarlais, J.R., and Zhukovsky, E.A. 2008 Potent in vitro and in vivo activity of an Fc-engineered anti-CD19. Cancer Res 68(19):8049-8057

Lawrence, C. E., Zalevsky, J., Horton, H., Leung, I., Chu, S., Karki, S., Zhukovsky, E., Desjarlais, J. R., & Carmichael, D. F. 2008 XmAb®5574, an Fc engineered humanized anti-CD19 monoclonal antibody, has potent in vitro and in vivo activities, and has the potential for treating B cell malignancies. Blood (poster) 112(11), 2621

Zalevsky, J., Leung, I.W., Karki, S., Chu, S.Y., Zhukovsky, E.A., Desjarlais, J.R., Carmichael, D.F., and Lawrence, C.E. 2009 The impact of Fc engineering on an anti-CD19 antibody: increased Fcγ receptor affinity enhances B-cell clearing in nonhuman primates. Blood 113:3735-3743

Awan, F.T., Lapalombella, R., Trotta, R., Butchar, J.P., Yu, B., Benson, D.M., Roda, J.M., Cheney, C., Mo, X., Lehman, A., Jones, J., Flynn, J., Jarjoura, D., Desjarlais, J.R., Tridandapani, S., Caligiuri, M.A., Muthusamy, N., and Byrd, J.C. 2010 CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain–engineered monoclonal antibody. Blood 115(6): 1204-1213

Kellner, C., Zhukovsky, E.A., Pötzke, A., Brüggemann, M., Schrauder, A., Schrappe, M., Kneba, M., Repp, R., Humpe, A., Gramatzki, M., and Peipp, M. 2013 The Fc-engineered CD19 antibody MOR208 (XmAb5574) induces natural killer cell-mediated lysis of acute lymphoblastic leukemia cells from pediatric and adult patients. Leukemia 27:1595-1598

Woyach, J.A., Awan, F., Flinn, I.W., Berdeja, J.G., Wiley, E., Mansoor, S., Huang, Y., Lozanski, G., Foster, P.A., and Byrd, J.C. 2014 A phase I trial of the Fc engineered CD19 antibody XmAb®5574(MOR00208) demonstrates safety and preliminary efficacy in relapsed chronic lymphocytic leukemia. Blood 124(24): 3553–3560

Immune Inhibitor Fc Domain

Chu, S.Y., Vostiar, I., Karki, S., Moore, G.L., Lazar, G.A., Pong, E., Joyce, P.F., Szymkowski, D.E., and Desjarlais, J.R. 2008 Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcγRIIb with Fc-engineered antibodies. Mol Immunol 45(15):3926-33

Horton, H.M., Chu, S.Y., Ortiz, E.C., Pong, E., Cemerski, S., Leung, I.W., Jacob, N., Zalevsky, J., Desjarlais, J.R., Stohl, W., and  Szymkowski, D.E. 2011 Antibody-mediated coengagement of FcγRIIb and B cell receptor complex suppresses humoral immunity in systemic lupus erythematosus. J Immunol 186(7):4223-33

Chu, S.Y., Yeter, K., Kotha, R., Pong, E., Miranda, Y., Phung, S., Chen, H., Lee, S.H., Leung, I., Bonzon, C., Desjarlais, J.R., Stohl, W., and Szymkowski, D.E. 2014 Suppression of rheumatoid arthritis B cells by XmAb5871, an anti-CD19 antibody that coengages B cell antigen receptor complex and Fcγ receptor IIb inhibitory receptor. Arthritis Rheumatol 66(5):1153-64

Szili, D., Cserhalmi, M., Bankó, Z., Nagy, G., Szymkowski, D.E., and Sármay, G. 2014 Suppression of innate and adaptive B cell activation pathways by antibody coengagement of FcγRIIb and CD19. mAbs 6(4):991-999

Xtend™ Fc Domain

Zalevsky, J., Chamberlain, A.K., Horton, H.M., Karki, S., Leung, I.W., Sproule, T.J., Lazar, G.A., Roopenian, D.C., and Desjarlais, J.R. 2010 Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 28(2):157-9

Bernett, M.J., Chu, S.Y., Leung, I., Moore, G.L., Lee, S.H., Pong, E., Chen, H., Phung, S., Muchhal, U.S., Horton, H.M., Lazar, G.A., Desjarlais, J.R., and Szymkowski, D.E. 2013 Immune suppression in cynomolgus monkeys by XPro9523: an improved CTLA4-Ig fusion with enhanced binding to CD80, CD86 and neonatal Fc receptor FcRn. mAbs 5(3):384-96

Saunders, K.O., Pegu, A., Georgiev, I.S., Zeng, M., Joyce, M.G., Yang, Z.Y., Ko, S.Y., Chen, X., Schmidt, S.D., Haase, A.T., Todd, J.P., Bao, S., Kwong, P.D., Rao, S.S., Mascola, J.R., and Nabel, G.J. 2015 Sustained delivery of a broadly neutralizing antibody in nonhuman primates confers long-term protection against simian/human immunodeficiency virus infection. J. Virol. 89(11):5895-5903

Nnane, I.P., Han, C., Jiao, Q., Tam, S.H., Davis, H.M., and Xu, Z. 2017 Modification of the Fc region of a human anti-oncostatin M monoclonal antibody for higher affinity to FcRn receptor and extension of half-life in cynomolgus monkeys. Basic Clin Pharmacol Toxicol doi:10.1111/bcpt.12761

XmAb® Core Technology

Lazar, G.A., Desjarlais, J.R., Jacinto, J., Karki, S., and Hammond P.W. 2007 A molecular immunology approach to antibody humanization and functional optimization. Mol Immunol 44, 1986-1998

Bernett, M.J., Karki, S., Moore, G.L., Leung, I.W., Chen, H., Pong, E., Nguyen, D.H., Jacinto, J., Zalevsky, J., Muchhal, U.S., Desjarlais, J.R., and Lazar, G.A. 2008 Engineering fully human monoclonal antibodies from murine variable regions. J Mol Biol 396(5):1474-90

Richards, J.O., Karki, S., Lazar, G.A., Chen, H., Dang, W., and Desjarlais, J.R. 2008 Optimization of antibody binding to FcγRIIa enhances macrophage phagocytosis of tumor cells. Mol Cancer Ther 7(8):2517-27

Moore, G.L., Chen, H., Karki, S., and Lazar, G.A. 2010 Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. mAbs 2(2):181-189

Cemerski, S., Chu, S.Y., Moore, G.L., Muchhal, U.S., Desjaralis, J.R., and Szymkowski, D.E. 2012 Suppression of mast cell degranulation through a dual-targeting tandem IgE–IgG Fc domain biologic engineered to bind with high affinity to FcγRIIb. Immunol Lett 143(1):34-43

Reviews

Desjarlais, J.R., Lazar, G.A., Zhukovsky, E.A., and Chu, S.Y. 2007. Optimizing engagement of the immune system by anti-tumor antibodies: an engineer’s perspective. Drug Discov Today 12(21-22): 898-910

Desjarlais, J.R., and Lazar, G.A. 2011. Modulation of antibody effector function. Exp Cell Res 317(9)1278-1285

Sondermann, P., and Szymkowksi, D.E. 2016. Harnessing Fc receptor biology in the design of therapeutic antibodies. Curr Opin Immunol 40:78-87

Clynes, R.A. and Desjarlais, J.R. 2019. Redirected T cell cytotoxicity in cancer therapy. Annu Rev Med. 70:437-450

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