A CellSqueeze®-Based Vaccine for Cancer Therapy Defne Yarar, Matt Booty, Alfonso Vincente-Suarez, Katarina Blagovic, Kelan Hlavaty, Scott Loughhead, Howard Bernstein, Armon Sharei SQZ Biotech, Watertown, MA
The development of effective vaccines that stimulate CD8 cytotoxic T lymphocyte (CTL) responses have been long sought after in the treatment of cancer. Previous efforts using antigen presenting cells (APCs) in the generation of vaccines have been hampered by the inherent difficulty in delivering antigen to the cell cytosol, a necessary step for CTL activation. To overcome this limitation, we use the CellSqueeze® delivery technology, which causes temporary membrane disruption as cells are passed through a microfluidic constriction. While the membrane is disrupted, cargo material in the surrounding buffer can diffuse directly into the cytosol. This methodology uniquely facilitates the loading of antigens into both conventional and unconventional antigen-presenting cells (APCs), including B cells and T cells, allowing the presentation of antigen on MHC-I molecules and the subsequent engagement with antigen-specific cytotoxic CD8 T lymphocytes. Here, we use this process to deliver cancer-associated antigens directly to the cytosol of APCs for the generation of cancer-targeted vaccines. Murine APC-based cancer vaccines processed with CellSqueeze® technology can stimulate antigen-specific CD8 T cell responses in vitro and in vivo. Furthermore, we demonstrate that vaccination of tumor bearing mice with these antigen-loaded APCs reduces tumor growth. We demonstrate that our vaccine alone or in combination with a checkpoint blocking antibody inhibits tumor growth in vivo. Finally, we demonstrate translation of these significant advantages of the technology to human APCs, which prime antigen-specific CD8 T cell responses in vitro. Collectively, these findings reinforce the clinical potential of CellSqueeze® for adoptive cell therapy in cancer treatment.
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