Preclinical Evaluation of Novel Folate Receptor 1-Directed CAR T Cells for Ovarian Cancer

• Published in: Cancers Vol. 16; no. 2; p. 333
• Main Authors: Daigre, Julie, Martinez-Osuna, Manuel, Bethke, Maria, Steiner, Larissa, Dittmer, Vera, Krischer, Katrin, Bleilevens, Cathrin, Brauner, Janina, Kopatz, Jens, Grundmann, Matthias David, Praveen, Paurush, Eckardt, Dominik, Bosio, Andreas, Herbel, Christoph
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.01.2024
• Subjects: Antibodies; Antigen (tumor-associated); Antigens; Ascites; Automation; cancer cell therapy; CAR T cells; cell surface targets; Chemotherapy; Chimeric antigen receptors; Consent; Cytokines; Cytotoxicity; Development and progression; Ethylenediaminetetraacetic acid; FDA approval; Folic acid; FOLR1; Genetically modified organisms; Glycoproteins; Immunosuppressive agents; immunotherapy; Lymphocytes; Lymphocytes T; Microscopy; Ovarian cancer; Patients; Plasmids; Solid tumors; T cells; Tumor cell lines; Tumor microenvironment; Vascular endothelial growth factor; Germany; cell surface targets; CAR T cells; ovarian cancer; immunotherapy; cancer cell therapy; solid tumor; FOLR1
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers16020333

Treatment options for ovarian cancer patients are limited, and a high unmet clinical need remains for targeted and long-lasting, efficient drugs. Genetically modified T cells expressing chimeric antigen receptors (CAR), are promising new drugs that can be directed towards a defined target and have shown efficient, as well as persisting, anti-tumor responses in many patients. We sought to develop novel CAR T cells targeting ovarian cancer and to assess these candidates preclinically. First, we identified potential CAR targets on ovarian cancer samples. We confirmed high and consistent expressions of the tumor-associated antigen FOLR1 on primary ovarian cancer samples. Subsequently, we designed a series of CAR T cell candidates against the identified target and demonstrated their functionality against ovarian cancer cell lines in vitro and in an in vivo xenograft model. Finally, we performed additional in vitro assays recapitulating immune suppressive mechanisms present in solid tumors and developed a process for the automated manufacturing of our CAR T cell candidate. These findings demonstrate the feasibility of anti-FOLR1 CAR T cells for ovarian cancer and potentially other FOLR1-expressing tumors.