Engineering of Tumor-Selective CAR for Adoptive Cell Therapy Against Kidney Cancer
Abstract
Advances in the treatment for renal cell carcinoma (RCC) have resulted in increased progression-free survival rate of many patients. However, the therapies are either toxic, or unable to achieve durable long-term complete responses. Carbonic anhydrase IX (CAIX), a tumor-associated antigen (TAA) overexpressed among serval solid tumor types, particularly in clear cell RCC, has been utilized in the design of chimeric antigen receptor (CAR) T cell therapies for metastatic clear cell RCC patients. Unlike the success shown in the CAR T therapies for hematological malignancies, the clinical development of CAIX CAR T therapy for RCC is limited by the "on-target off-tumor" toxicity and immunosuppressive signaling from the tumor microenvironment. We tested the approach for designing the masked CAIX CARs with the attempt to improve its tumor selectivity. The masked CAR can be successfully constructed and their expression was observed in T cells. However, even with incorporated masking peptides, this CAR lacked the masking effect. We also demonstrated the potential of anti-PD1 trap protein self-secreting CAR-T as a potential cancer immunotherapy therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2020
- Accession Number
- AD1148577
Entities
People
- Pin Wang
Organizations
- University of Southern California