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Tumor-Specific Cancer Vaccine Adjuvant Formulation

Interests: Oncology, Vaccines
Published:
Lead Inventor: Jeffrey Hubbell
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SUMMARY

  • Many cancer vaccines fail due to insufficient CD8+ T cell targeting.  To save patient lives, oncologists need tumor-specific vaccines that increase CD8+ T cell response.
  • The inventors developed and validated an intra-tumoral vaccine adjuvant for muringe melanoma.  They used a p(ManTLR7) glyco-polymer to chemically link to tumor cell binding moieties (i.e., (f(ab)2, fAb, scFv, etc.).  Their adjuvant conjugation Anti-p(Man-TLR7) augmented tissue localization and biodistribution.
  • Anti-p(Man-TLR7) builds on earlier use of p(Man-TLR7) as a priming agent for strong CD8+ T cell responses to traditional model antigens and malaria vaccination models.
  • The team's in vivo experiments with B16F10 tumor-bearing mice demonstrated that Anti-p(ManTLR7) outperforms CpG, a TLR9 stimulating adjuvant, for tumor size reduction and survival rate.

FIGURE

A) Mice tissue retains anti-TRP1-pManTLR7 intratumorally. During imaging studies, 30μg of fluorescently labeled anti-TRP1- pManTLR7 were injected intratumorally 5 days after B16F10 tumor inoculation (4×105 cells).  Tumor growth slowed significantly.  B) Anti-TRP1-pManTLR7 treatment reduces B16F10 melanoma growth rates, systemic exposure to TLR7 and overall death rates.  Note that 50% of all Anti-TRP1-pManTLR7 treated mice survived to Day 20.  No mice who received unconjugated treatment, on the other hand, were alive on 20.

ADVANTAGES

ADVANTAGES

  • The tumor serves as a source of antigen to which immune responses are generated.
  • Based on CpG's track record, this approach is scalable from melanoma to breast cancer, colon cancer, glioblastoma, lymphoma, sarcoma, and ovarian cancer.
  • Anti-TRP1-pManTLR7 exhibits low potential for off-target effects and overall tolerability.

APPLICATIONS

  • Monotherapy
  • Immune checkpoint inhibitors

 

  • Iteration of Hubbell Lab Patent WO2017058996A1