Chimeric Switch Receptors to Potentiate CAR T Cell Therapy for Solid Tumor Cancers

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Project Abstract/Summary Cancer is expected to claim 8.8 million lives worldwide this year. In the US, it is the leading cause of death with a prevalence that continues to grow each year. Conventional treatment options tend to be limited in efficacy and are often accompanied by deleterious side effects. Newer antibody-based and cell-based therapies have shown particular promise for a subset of solid tumor and hematological cancers, respectively. Importantly, while these new therapies have shown promise, they are often only effective in a small cross-section of patients or are accompanied by severe side effects. Solid tumor cancer patients tend to have the poorest prognoses and outcomes. This is likely due strong suppression of patients’ immune systems driven by cancer cell signaling. This proposal aims to overcome key mechanisms of immune suppression in the tumor microenvironment to unlock the full potential of new classes of cancer therapeutics. Importantly, the technology leverages alternative signaling pathways which show promise for enhancing immune system function. With this Phase I SBIR, Javelin Oncology intends to provide preclinical proof-of-concept that a novel therapeutic can enhance the function of the current generation of cellular therapies to unlock their potential for treating solid cancers. These experiments will drive the selection of a lead therapeutic and justify the IND- enabling preclinical work required to prepare these novel therapeutics for delivery to patients.