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Updated: Sep 15, 2025
Author Spotlight: Enhancing CAR-T Cell Function in Syngeneic Tumor Models
Published on: February 2, 2024
IL-7 armed binary CAR T cell strategy to augment potency against solid tumors
Alejandro G Torres Chavez1, Mary K McKenna1, Anmol Gupta2
1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Abstract:
Clinical studies of T cells engineered with chimeric antigen receptor (CAR) targeting CD19 in B-cell malignancies have demonstrated that relapse due to target antigen (CD19) loss or limited CAR T cell persistence is a common occurrence. The possibility of such events is greater in solid tumors, which typically display more heterogeneous antigen expression patterns and are known to directly suppress effector cell proliferation and persistence. T cell engineering strategies to overcome these barriers are being explored. However, strategies to simultaneously address both antigen heterogeneity and T cell longevity, while localizing anti-tumor effects at disease sites, remain limited. In this study we explore a dual antigen targeting strategy by directing independent CARs against the solid tumor targets PSCA and MUC1. To enhance functional persistence in a tumor-localized manner, we expressed the transgenic IL-7 cytokine and receptor (IL-7Rα) in respective CAR products. We now demonstrate the potency and durable antitumor effects of this binary strategy in a pancreatic tumor model.
Insights
This study introduces a novel dual CAR T cell therapy targeting PSCA and MUC1 to overcome antigen loss in solid tumors. The engineered T cells, expressing IL-7 and IL-7Rα, demonstrated potent and durable anti-tumor effects in pancreatic cancer models.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Engineering
Background:
- Chimeric antigen receptor (CAR) T cell therapy shows promise for B-cell malignancies but faces challenges in solid tumors.
- Relapse in CAR T cell therapy often results from antigen loss and poor T cell persistence.
- Solid tumors present unique barriers including antigen heterogeneity and immune suppression, limiting CAR T cell efficacy.
Purpose of the Study:
- To develop a dual CAR T cell strategy targeting both PSCA and MUC1 to address antigen heterogeneity in solid tumors.
- To enhance T cell persistence and anti-tumor activity within the tumor microenvironment.
- To evaluate the efficacy of this binary CAR T cell approach in a preclinical pancreatic cancer model.
Main Methods:
- Engineering T cells with independent CARs targeting PSCA and MUC1.
- Co-expression of transgenic IL-7 cytokine and receptor (IL-7Rα) to promote localized T cell persistence.
- Assessment of the dual CAR T cell strategy's potency and durability in a pancreatic tumor model.
Main Results:
- The dual CAR T cell strategy effectively targeted both PSCA and MUC1 antigens.
- Engineered T cells exhibited enhanced persistence and localized anti-tumor activity.
- Demonstrated potent and durable antitumor effects in the pancreatic tumor model.
Conclusions:
- A dual CAR T cell strategy targeting PSCA and MUC1, combined with IL-7/IL-7Rα co-expression, offers a promising approach for solid tumors.
- This binary strategy effectively overcomes antigen heterogeneity and enhances T cell longevity.
- The findings support the potential of this enhanced CAR T cell therapy for pancreatic cancer treatment.
