The development of targeted immunotherapy has become a cornerstone of cancer treatment over the past decades. Chimeric Antigen Receptor (CAR) T-cells are one of the modalities that were effective in hematologic cancers yet the translation of its success in solid tumors remains a formidable challenge. Solid tumors with low immunogenicity, heterogenous cancer antigen expression and an evasive tumor microenvironment pose significant clinical challenges to CAR-T cells, leading to treatment resistance and limited response durability. To address the growing medical unmet needs for solid tumor therapy, we have developed PST1xPST7 bispecific CAR-T cells, targeting co-localized oncogenic proteins associated with cancer malignancy and chemoresistance.
We demonstrate that the spatial arrangement and relative orientation of targeting antibodies in bispecific CAR-T cells are vital for therapeutic efficacy. Our findings reveal that bispecific CAR-T cells exhibit potent cytolytic activity against target cancer cells, outperforming monospecific CAR-Ts. This dual-targeting approach addresses issues of antigen escape and cancer relapse, offering a more effective strategy to combat and mitigate relapse associated with antigen loss.
Bispecific CAR-T cells targeting PST1 and PST7 enhance immunotherapy efficacy, providing a robust and durable anti-tumor response. This innovative strategy represents a significant advancement in cancer treatment, addressing the urgent need for improved therapeutic options.