Multi-Pass Scaffold Technology for Modular CAR T-Cell Therapies

Stanford researchers have developed the Broadly Usable Multi-Pass Engineered Receptor (BUMPER) architecture, a novel protein engineering platform for assembling stable, multifunctional cell surface receptors. BUMPER technology enables separate anchoring of multiple functional domains, such as antigen-binding regions, within distinct transmembrane segments of a single protein — reliably supporting homogeneous expression and overcoming misfolding and domain-interference issues commonplace in current multi-specific chimeric antigen receptor (CAR) T-cell therapies.

Single-target CAR T therapies for cancer have exhibited promise but often fail in solid tumors due to antigen loss and tumor heterogeneity, prompting the need for multi-specific approaches. Existing methods to generate multi-targeting CAR T cells face challenges including decreased expression, misfolding, and unpredictable efficacy, particularly when combining multiple binding domains in a single protein. BUMPER eliminates these issues by providing a modular, plug-and-play scaffold for integration of diverse protein domains at flexible sites and spacings, all while supporting robust in vivo expression and performance.

The inventors' stable scaffold architecture supports efficient production of multifunctional proteins that maintain in vivo efficacy, expanding possibilities for next-generation CAR T therapies targeting multiple tumor antigens simultaneously, as well as broader applications in immune cell signaling and therapeutic protein delivery.

Stage of Development
Preclinical, with in vitro and in vivo validation data obtained