Targeting multiple solid tumor types with anti-CD70 allogeneic CAR-T cells

CD70 (CD27 ligand) is highly expressed in multiple hematologic malignancies, such as non-Hodgkin lymphoma, multiple myeloma, and chronic lymphocytic leukemia, and is uniquely highly expressed in the solid tumor type clear cell renal cell carcinoma (ccRCC). Malignancies showing high CD70 expression have been the subject of multiple clinical trials evaluating anti-CD70 agents, such as antibodies with enhanced antibody-dependent cell-mediated cytotoxicity and antibody drug conjugates (ADCs). The focus on high expression indications seems to be a requirement, particularly for ADCs. We have shown previously that CTX130, a CRISPR/Cas9 gene-edited allogeneic anti-CD70 CAR-T, is potently cytotoxic against even the lowest expressing RCC cells (e.g. ACHN). With this in mind, we evaluated CD70 expression in other solid tumor indications, including pancreatic, lung, and ovarian cancers, and assessed the cytotoxic activity of CTX130 against cell lines derived from these tumor types. These studies show that high expression is not a requirement for potent activity for CAR-T cells as it appears to be for CD70-targeted ADCs. Further, these data highlight a translational medicine route for CTX130 in many solid tumor indications. Citation Format: Mary Lee Dequeant, Sushant Karnik, Zinkal Padalia, Minh Thu Tham, Tony Ho, Julie Carson, Jonathan A. Terrett. Targeting multiple solid tumor types with anti-CD70 allogeneic CAR-T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3184.