Abstract 6595: Targeting T cell lymphomas with CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells

T cell lymphomas account for 10% to 15% of non-Hodgkin lymphomas and are diverse biologically and clinically. Unlike B-cell lymphomas, T cell lymphomas are rather resistant to conventional therapies, such as chemotherapy and antibody-based therapeutics. This resistance coupled with the diversity of the T cell diseases means that there is a significant unmet need across the T cell lymphoma subtypes. CD70 (CD27 ligand) is a candidate target antigen for T cell lymphomas and has been is the subject of clinical trials using an enhanced ADCC antibody (ARGX-110). Using flow cytometry and immunohistochemistry (IHC) methods, we analyzed the expression of CD70 in cell lines and clinical samples representing T cell lymphomas and found significant expression of CD70 in multiple types of T cell lymphoma, but at highly variable antigen density. CAR-T cells targeting CD70 may thus be a potent new therapy to tackle these diseases. However, the use of autologous CAR-T therapy against T cell lymphomas is complicated by the likelihood of creating lymphoma cells carrying the CAR construct. Thus, we sought to examine the potency of our allogeneic anti-CD70 CAR-T cells (CTX130) against T cell lymphoma cells. CTX130 has previously been shown to be active across a range of CD70 expression levels in other cell types representing other malignancies. Consistent with these prior observations, CTX130 exhibited high potency in vitro and in vivo against T cell lymphoma cells across a range of CD70 antigen density and representing different types of T cell lymphomas such as Sezary syndrome and cutaneous T cell lymphoma (CTCL). CTX130 may thus be a valid therapeutic to evaluate in T cell lymphoma patients. Citation Format: Sushant Karnik, Minh Thu Pham, Pooja Keerthipati, Zinkal Padalia, Julie Carson, Tony Ho, Ewelina Morawa, Matthias Will, Jonathan Terrett, Mary-Lee Dequeant. Targeting T cell lymphomas with CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6595.