Protein-Chaperoned T-Cell Vaccines

Technology #18577

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Mouse serum albumn fusion strategy improves the potency of E7(38-57).
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Inventors
Professor Darrell Irvine
Department of Biological Engineering, MIT
External Link (irvine-lab.mit.edu)
Professor Karl Wittrup
Department of Chemical Engineering, MIT
Kavya Rakhra
Koch Institute for Integrative Cancer Research, MIT
Naveen Mehta
Department of Biological Engineering, MIT
Eric Zhu
Department of Chemical Engineering, MIT
Managed By
Jon Gilbert
MIT Technology Licensing Officer
Patent Protection

Protein-Chaperoned T-Cell Vaccines

Provisional Patent Application Filed

Applications

This technology increases the potency of cancer vaccines.

Problem Addressed

There is only one FDA approved cancer vaccine, Sipuleucel-T, which only provides a modest survival benefit from prostate cancer. Sipuleucel-T depends on the manipulation of a patient’s own immune cells, and therefore suffers from logistical difficulties that create barriers to its widespread adaptation. Conversely, more logistically feasible peptide-based cancer vaccines have response rates of merely 3-5%.  This technology is a generalizable strategy to improve the potency of peptide-based cancer vaccines.

Technology

A common issue with current peptide vaccines is the inability to traffic to the secondary lymphoid organs.  This technology uses protein chaperones to improve bioavailability in the lymph node following subcutaneous injection. T-cell epitopes (antigens) are fused to protein chaperones to form chaperone-antigens and delivered together with an adjuvant. This vaccine can also be combined with other immunotherapy modalities composed of a tumor targeting antibody, an extended serum half-life IL-2, and checkpoint inhibitor antibodies like anti-PD-1 and anti-CTLA4. The strategy of targeting the lymph nodes also avoids circulatory uptake. The inventors have shown potent anti-tumor CD8+ T-cell responses, which cause regression of 80% of mice bearing large established tumors. The E738-57 peptide and CDN adjuvant vaccine consistently generates weak responses: 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 approximately 7.5%, closer to the frequency one would expect in a natural infection. This strategy is compatible with multiple protein carriers and adjuvants.

Advantages

  • Increases potency of peptide vaccines
  • Avoids circulatory uptake
  • Different protein carriers or adjuvants may be incorporated into the design