Publications

Programs

CD3 Bispecific Antibodies

Tumor Microenvironment Activating Bispecific Antibodies

Engineered Cytokines

Preclinical-stage Platforms

Plamotamab (CD20 x CD3 Bispecific Antibody)

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)

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

Additional XmAb® 2+1 Bispecific Antibody Programs

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

Nisthal, A., et al. 2021, American Association for Cancer Research (poster). Affinity tuned XmAb® 2+1 GPC3 x CD3 bispecific antibodies demonstrate selective activity in liver cancer models

Nisthal, A., et al. 2020, American Association for Cancer Research (poster). Affinity tuned XmAb®2+1 PSMA x CD3 bispecific antibodies demonstrate selective activity in prostate cancer models

Zeng, V. G., et al. 2020, American Association for Cancer Research (poster). Affinity tuned XmAb® 2+1 anti-mesothelin x anti-CD3 bispecific antibody induces selective T cell-dependent cellular cytotoxicity of human ovarian cancer cells

Vudalimab (PD-1 x CTLA-4 Bispecific Antibody)

Shum, E., et al. 2021, Society for Immunotherapy of Cancer (poster). Preliminary Clinical Experience With Vudalimab, a PD-1 x CTLA-4 Bispecific Antibody, in Patients With Advanced Solid Tumors

Shum, E., et al. 2020, Society for Immunotherapy of Cancer (poster). Preliminary Safety, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of XmAb®20717, a PD-1 x CTLA-4 Bispecific Antibody, in Patients With Advanced Solid Tumors

Hedvat, M., et al. 2018, Society for Immunotherapy of Cancer (poster). Simultaneous checkpoint – costimulatory or checkpoint – checkpoint receptor targeting with bispecific antibodies promotes enhanced human T cell activation

Hedvat, M., et al. 2018, American Association for Cancer Research (poster). Simultaneous checkpoint-checkpoint or checkpoint-costimulatory receptor targeting with bispecific antibodies promotes enhanced human T cell activation

Hedvat, M., et al. 2017, Society for Immunotherapy of Cancer (poster). Dual Blockade of PD1 and CTLA4 with Bispecific Antibody XmAb20717 Promotes Human T Cell Activation and Proliferation

Hedvat, M., et al. 2016, J Immunother Cancer (poster) 4(Suppl 1):82. Dual blockade of PD-1 and CTLA-4 with bispecific antibodies promotes human T cell activation and proliferation.

Bernett, M. J., et al. 2016, J Immunother Cancer (poster) 4(Suppl 1):82 Multiple bispecific checkpoint combinations enhance T cell activity.

XmAb®104 (PD-1 x ICOS Bispecific Antibody)

Hedvat, M., et al. 2018, Society for Immunotherapy of Cancer (poster). Simultaneous checkpoint – costimulatory or checkpoint – checkpoint receptor targeting with bispecific antibodies promotes enhanced human T cell activation

Hedvat, M., et al. 2018, American Association for Cancer Research (poster). Simultaneous checkpoint-checkpoint or checkpoint-costimulatory receptor targeting with bispecific antibodies promotes enhanced human T cell activation

Moore, G. L., et al. 2017, Society for Immunotherapy of Cancer (poster). Anti-PD1 x anti-ICOS bispecific antibody XmAb23104 brings together PD1 blockade and ICOS costimulation to promote human T cell activation and proliferation

Moore, G. L., et al. 2017, American Association for Cancer Research (poster). Combination of PD1 blockade and T cell costimulation by bispecfic antibodies promotes human T cell activation and proliferation

XmAb®306 (IL15/IL15Rα-Fc Cytokine)

Bernett, M. J., et al. 2018, Society for Immunotherapy of Cancer (poster). An IL15/IL15Rα heterodimeric Fc-fusion engineered for reduced potency demonstrates an optimal balance of in vivo activity and exposure

Bernett, M. J., et al. 2018, American Association for Cancer Research (poster). Potency-reduced IL15/IL15Rα heterodimeric Fc-fusions display enhanced in vivo activity through increased exposure

Bernett, M. J., et al. 2017, American Association for Cancer Research (poster). IL15/IL15Rα heterodimeric Fc-fusions with extended half-lives

XmAb®564 (IL2-Fc Cytokine)

Varma, R., et al. 2018, American Society of Hematology (poster). Regulatory T cell selective IL-2-Fc fusion proteins for the treatment of autoimmune disease

XmAb®662 (IL12-Fc Cytokine)

Bernett, M. J., et al. 2021, Society for Immunotherapy of Cancer (poster). IL12 Fc-fusions engineered for reduced potency and extended half-life exhibit strong anti-tumor activity and improved therapeutic index compared to wild-type IL12 agents

Bernett, M. J., et al. 2021, American Association for Cancer Research (poster). IL12 heterodimeric Fc-fusions engineered for reduced potency exhibit strong anti-tumor activity and improved therapeutic index compared to native IL12 agents

Bernett, M. J., et al. 2020, Society for Immunotherapy of Cancer (poster). Potency-reduced and extended half-life IL12 heterodimeric Fc-fusions exhibit strong anti-tumor activity with potentially improved therapeutic index compared to native IL12 agents

Varma, R., et al. 2020, American Association for Cancer Research (poster). Potency-reduced IL12 heterodimeric Fc-fusions exhibit strong anti-tumor activity

Additional Cytokine Programs

Nisthal, A., et al. 2022, American Association for Cancer Research (poster). Engineered IL18 heterodimeric Fc-fusions featuring improved stability, reduced potency, and insensitivity to IL18BP

Bernett, M., et al. 2022, American Association for Cancer Research (poster). LAG3-targeted IL15/IL15Rα-Fc (LAG3 x IL15) fusion proteins for preferential TIL expansion

CD28 Bispecific Antibody Platform

Zeng, V. G., et al. 2021, Society for Immunotherapy of Cancer (poster). PDL1-targeted CD28 costimulatory bispecific antibodies enhance T cell activation in solid tumors

Moore, G., et al. 2021, American Association for Cancer Research (poster). PDL1-targeted 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

TGFβ Bispecific Antibody Platform

Moore, G. L., et al. 2021, Society for Immunotherapy of Cancer (poster). PD1 x TGFβR2 and CD5 x TGFβR2 bispecifics selectively block TGFβR2 on target-positive T cells, promote T cell activation, and elicit an anti-tumor response in solid tumors

Moore, G. L., et al. 2020, Society for Immunotherapy of Cancer (poster). PD1 x TGFβR2 bispecifics selectively block TGFβR2 on PD1-positive T cells, promote T cell activation, and elicit an anti-tumor response in solid tumors

NK Cell Engager Bispecific Antibody Platform

Bykova, K., et al. 2021, Society for Immunotherapy of Cancer (poster). Natural killer cell engagers activate innate and adaptive immunity and show synergy with proinflammatory cytokines

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

Chu, S. Y., Miranda, Y., Phung, S., Chen, H., Rashid, R., Endo, N. A., Chan, E. W., Pong, E., Bonzon, C., Muchhal, U. S., Leung, I. W., Bernett, M. J., Moore, G. L., Szymkowski, D. E., and Desjarlais, J. R. 2014. Immunotherapy with long-lived anti-CD38 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human myeloma cell lines and CD38+ cells in monkeys: a potential therapy for multiple myeloma. Blood (poster) 124(21), 4727

Chu, S. Y., Pong, E., Chen, H., Phung, S., Chan, E. W., Endo, N. A., Rashid, R., 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-CD123 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human AML cell lines and of CD123+ cells in monkeys: a potential therapy for acute myelogenous leukemia. Blood 124(21), 2316

Moore, G. L., Lee, S., Schubbert, S., Miranda, Y., Rashid, R., Pong, E., Phung, S., Chan, E. W., Chen, H., Endo, N., Ardila, M. C., Bernett, M. J., Chu, S., Leung, I. W., Muchhal, U., Bonzon, C., Szymkowski, D. E., and Desjarlais, J. 2015. Tuning T cell affinity improves efficacy and safety of anti-CD38 × anti-CD3 bispecific antibodies in monkeys – a potential therapy for multiple myeloma. Blood (poster) 126(23), 1798

Chu, S.Y., Pong, E., Schubbert, S., Rashid, R., Chen, S., Chan, E., Phung, S., Endo, N.A., Ardilla, M.C., Bonzon, C., Leung, I.W.L., Muchhal, U.S., Moore, G.L., Bernett, M.J., Avery, K.A., Desjarlais, J.R. and Szymkowski, D.E. 2016. Immunotherapy with anti-PSMA x anti-CD3 bispecific antibody stimulates potent killing of a human prostate cancer cell line and target-mediated T cell activation in monekys: a potential therapy for prostate cancer. Cancer Res 76(14)Suppl

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

Lee, S-H., Chu, S.Y., Rashid, R., Phung, S., Leung, I., Muchhal, U.S., Moore, G.L., Bernett, M.J., Schubbert, S., Ardila, C., Bonzon, C., Foster, P., Szymkowski, D.E., and Desjarlais, J.R. 2017. Anti-SSTR2 × anti-CD3 bispecific antibody induces potent killing of human tumor cells in vitro and in mice, and stimulates target-dependent T cell activation in monkeys: a potential immunotherapy for neuroendocrine tumors. AACR Annual Meeting (poster)

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

Lawrence, C. E., Hammond, P. W., Zalevsky, J., Horton, H., Chu, S., Karki, S., Desjarlais, J. R., and Carmichael, D. F. 2007 XmAb™2513, an Fc engineered humanized anti-CD30 monoclonal antibody, has potent in vitro and in vivo activities, and has the potential for treating hematologic malignancies. Blood (poster) 110(11), 2340

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

Horton, H. M., Bernett, M. J., Peipp, M., Pong, E., Karki, S., Chu, S. Y., Richards, J. O., Chen, H., Repp, R., Desjarlais, J. R., and Zhukovsky, E. A. 2010 Fc-engineered anti-CD40 antibody enhances multiple effector functions and exhibits potent in vitro and in vivo antitumor activity against hematologic malignancies. Blood 116(16), 3004-3012

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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