Protein-Chaperoned T-Cell Vaccines

Applications

This technology increases the potency of cancer vaccines.

Problem Addressed

To date, Sipuleucel-T is the only FDA approved cancer vaccine, which only provides a modest survival benefit in patients with prostate cancer. As an autologous cell-based vaccine, Sipuleucel-T and proposed therapies like it suffer from logistical difficulties that create barriers to its widespread adaptation. Conversely, more logistically feasible peptide-based cancer vaccines have low response rates. This technology is a generalizable strategy to improve the potency of peptide-based cancer vaccines

Technology

A common issue with peptide vaccines is their inability to reach lymph nodes, where immune responses are orchestrated. In this technology, T-cell epitopes (antigens) are fused to protein chaperones to form chaperone-antigen fusions, which are of appropriate size to avoid circulatory uptake and instead target the lymphatics. The E738-57 peptide and cyclic dinucleotide adjuvant vaccine is weak: following vaccination, less than 0.5% of circulating CD8 T-cells are E7-specific. With a mouse serum albumin protein chaperone, however, the response increases to 7.5%, closer to the frequency one would expect in a natural infection. This strategy is modular and can easily be modified for the desired protein carrier, antigen, and adjuvant. The subunit vaccine can also be combined with other immunotherapy modalities including a tumor targeting antibody, an extended serum half-life IL-2, and checkpoint inhibitor antibodies like anti-PD-1 and anti-CTLA4. The inventors have shown potent anti-tumor CD8+ T-cell responses, which induce regression in 80% of mice bearing large established tumors. This strategy extends to other genetically encodable vaccine modalities, including DNA and RNA vaccines, whereby in vivo transfection of constructs that encode chaperone-antigen fusions induce immunological responses.

Advantages

  • Increases potency of peptide vaccines
  • Generalizable strategy for many antigens of interest
  • Enables multiple vaccine modalities: DNA, RNA, protein vaccines