Abstract 3243: Allogeneic anti-PTK7 CAR-T cells for the treatment of solid tumors

Abstract

Abstract Protein Tyrosine Kinase 7 (PTK7), also known as colon cancer carcinoma kinase 4 (CCK-4), is a highly conserved catalytically inactive tyrosine kinase with inherent signal transduction activity. PTK7 is a member of the Wnt signaling pathway and thought to function in cell proliferation, adhesion, migration and apoptosis. PTK7 has been shown to be highly expressed in certain cancer types including colon, breast, lung, pancreatic, renal and ovarian. Downregulation of PTK7 by shRNA has been shown to reduce tumor growth and metastases development in xenograft mouse models. Furthermore, high PTK7 expression in triple negative breast cancer and NSCLC patients has been linked to poor prognosis. PTK7 therefore appears to be an attractive target for solid cancer therapeutic intervention and has been targeted clinically with an Antibody Drug Conjugate (PF-06647020). However, the protein is also expressed to a lesser degree in some normal adult tissues, particularly in the stromal cells of the ovary, placenta, uterus and lung. We have developed a human/murine cross-reactive anti-PTK7 CAR construct and assessed the ability of allogeneic anti-PTK7 CAR-T cells bearing that construct to target cancer cells and elicit toxicity in mice. These anti-PTK7 CAR-T cells were shown to be efficacious in vitro and in immunocompromised mouse xenograft models of breast, lung, colon, pancreatic and ovarian cancer. However, consistent in all xenograft models studied, a drop in body weight was observed shortly after injection from which all mice rapidly recovered to above baseline. Latent toxicity that was more variable amongst the xenograft experiments was also observed. Understanding and developing appropriate mitigation strategies to address the observed toxicities may be required to develop further a safe and efficacious allogeneic anti-PTK7 CAR-T cell therapy for solid tumor cancers. Citation Format: Katie Levitsky, Zejun Li, Minh Thu Pham, Kelly Maeng, Luke Hanley, Jason Sagert, Jon Terrett, Jui Dutta-Simmons, Melanie Allen. Allogeneic anti-PTK7 CAR-T cells for the treatment of solid tumors [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 3243.