Effect of placental circulating T cells expressing CD16 on multiple hematological and solid tumor cancers through combination with various monoclonal antibodies.

person Kathy Karasiewicz-Mendez Celularity Inc., Florham Park, NJ info_outline Kathy Karasiewicz-Mendez, Kristina Tess, Mansour Djedaini, Chenfei Huang, Joseph Gleason, Shengchen Lin, Natalia Ruggeri Barbaro, John Fitzgerald, Shuyang He, Robert Hariri, Adrian Kilcoyne

Authors person Kathy Karasiewicz-Mendez Celularity Inc., Florham Park, NJ info_outline Kathy Karasiewicz-Mendez, Kristina Tess, Mansour Djedaini, Chenfei Huang, Joseph Gleason, Shengchen Lin, Natalia Ruggeri Barbaro, John Fitzgerald, Shuyang He, Robert Hariri, Adrian Kilcoyne Organizations Celularity Inc., Florham Park, NJ, Celularity Inc, Florham Park, NJ Abstract Disclosures Research Funding Celularity Inc Background: PT-CD16VS is an allogeneic cell therapy derived from human postpartum placental circulating T (PT) cells that are genetically modified to express CD16 and endogenous T cell receptor (TCR) knockout. PT-CD16VS cells can be combined with various monoclonal antibodies to engage in anti-tumor antibody-dependent cellular cytotoxicity (ADCC) against diverse cancers with a “universal receptor” approach. Here we report the characterization and preclinical evaluation of PT-CD16VS in combination with monoclonal antibodies against both hematological and solid tumor cancers. Methods: PT cells were activated, transduced with a lentiviral vector containing a construct expressing a high affinity CD16 variant, CD16VS, and transfected to knock out the TCR. In vitro, functional activity of PT-CD16VS cells in combination with monoclonal antibodies was assessed in cytotoxicity, cytokine release, and proliferation assays. In vivo, PT-CD16VS was combined with Rituximab in a Raji xenograft model in NSG mice, and with Trastuzumab in a subcutaneous NCI-N87 xenograft model in NSG mice in which tumor volume was measured and tumor samples were evaluated for PT-CD16VS infiltration. Results: In vitro , PT-CD16VS exhibited potent ADCC and cytokine release when combined with Rituximab against CD20+ Burkitt's lymphoma (Daudi and Raji), with Trastuzumab against HER2+ gastric carcinoma (NCI-N87), with Trastuzumab or Avelumab against HER2+/PDL-1+ non-small cell lung carcinoma (NCI-H1975) and Trastuzumab-resistant metastatic mammary adenocarcinoma (JIMT-1), and with Cetuximab against EGFR+ triple negative metastatic mammary adenocarcinoma (MDA-MB-231). Moreover, examples of PT-CD16VS antigen-specific proliferation were demonstrated against Raji and NCI-N87 when cells were combined with Rituximab and Trastuzumab, respectively. In vivo , in combination with Rituximab in the Raji mouse model, PT-CD16VS exhibited significant survival benefit compared to vehicle and Rituximab alone treated groups. In the subcutaneous NCI-N87 solid tumor model, PT-CD16VS with Trastuzumab demonstrated significant reduction in tumor volume compared to vehicle, Trastuzumab, and Enhertu groups. In addition, PT-CD16VS infiltration into the tumor was shown to be Trastuzumab dependent, with infiltrating cells expressing high levels of CD16 and Ki67. Conclusions: Our results show that PT-CD16VS have potent in vitro and in vivo ADCC activity, and a single drug product has the potential to be combined with various monoclonal antibodies to target multiple cancers across hematological and solid tumor indications. This “universal receptor” with antibody-dependent targeting approach, together with the benefits of an allogeneic cell platform, may democratize accessibility of such therapies for patients.