432 Evaluation of novel anti-TIGIT antibody M6223 as a single agent and in combination with avelumab on human natural killer (NK) cell cytotoxicity

BackgroundM6223 is a fully human antagonistic anti-TIGIT immunoglobulin (Ig) G1 antibody with fragment crystallizable (Fc)-mediated effector function. Preclinical studies demonstrated that M6223 could induce an anti-tumor immune response through several mechanisms, including direct blockade of the T...

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Bibliographic Details
Published in:Journal for immunotherapy of cancer 2022-11, Vol.10 (Suppl 2), p.A453-A453
Main Authors: Titov, Anton, Sun, Nancy, Kelton, Christie, Jurzak, Mirek, Ma, Hong, Xu, Chunxiao
Format: Article
Language:English
Subjects:
Antibodies
Bladder cancer
Cancer
Cytotoxicity
Immunotherapy
Kidney cancer
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Summary:BackgroundM6223 is a fully human antagonistic anti-TIGIT immunoglobulin (Ig) G1 antibody with fragment crystallizable (Fc)-mediated effector function. Preclinical studies demonstrated that M6223 could induce an anti-tumor immune response through several mechanisms, including direct blockade of the TIGIT pathway, stimulation of CD226 dimerization/activation, and depletion of TIGIT+ immune subsets by Fc-mediated effector function. Avelumab is a human IgG1 anti–PD-L1 antibody with a wild-type Fc region that has been shown to induce antitumor activity in vitro via both adaptive effector cells (T cells) and innate immune effector cells (antibody-dependent cell-mediated cytotoxicity [ADCC] via NK cells). It is approved for urothelial carcinoma (UC), renal cell carcinoma, and Merkel cell carcinoma. We report an evaluation of the effects of M6223 as a single agent and in combination with avelumab on human NK cell cytotoxicity.MethodsNK cell anti-tumor cytotoxicity was measured against the cancer line MDA-MB-231 with beta-2 microglobulin (B2M) knockout using fluorescent live cell imaging. NK cells were treated with M6223 or its Fc effector null version PPB1791. Avelumab was also tested alone or at a single dose combination with M6223 to evaluate additive potential of these antibodies. A variety of CD155 (poliovirus receptor [PVR]) knockout and partial knockouts were generated to assess the dependence of anti-tumor cytotoxicity on expression of this ligand.ResultsM6223 induced significant NK cell anti-tumor cytotoxicity in 4 different NK donors at doses above 0.3 mcg/mL (t-test: p
ISSN:2051-1426
DOI:10.1136/jitc-2022-SITC2022.0432