# A Cobalt Porphyrin Nanoliposome Adjuvant for MHC-I-Restricted Cancer Peptide Vaccines

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $370,870

## Abstract

PROJECT SUMMARY
MHC class I (MHC-I) -restricted peptide cancer vaccines hold the minimal amount of biochemical information
required for generating antigen-specific T cells to elicit anti-tumor responses. On their own, immunization with
minimal peptide epitopes does not provide a satisfactory response, so typically long peptides or conjugated
delivery systems are necessitated. However, such approaches defeat the directness of short synthetic peptide
vaccines. A new peptide vaccine immunization paradigm will be introduced, based on combining (via simple
mixing) MHC-I peptide epitopes with a vaccine adjuvant that induces spontaneous nanoliposome-antigen
particleization (SNAP). Liposomes that contain small amounts of cobalt porphyrin-phospholipid (CoPoP) rapidly
bind short his-tagged peptides (8-9mers) via spontaneous insertion of the his-tag into the bilayer. This gives rise
to particleization that is stable in biological media. His-tagged peptides are simply mixed with CoPoP liposomes
at the time of vaccination (without further purification) to convert these well-characterized peptides into a 100 nm
particle. This approach is potently effective in generating antigen-specific CD8+ T cells. AH1 is a MHC-I H-2Ld
model CD8+ epitope derived from the gp70 murine leukemia virus antigen. An AH1-derived peptide can be used
with SNAP immunization to generate high numbers of antigen specific CD8+ T cells. SNAP immunization with
low nanogram doses peptides completely protects mice from subsequent tumor challenge, and eradicates 100%
of lung metastases in a therapeutic vaccine model. Varying components of SNAP immunization will be assessed,
including the his-tag length, the density and dose of co-incorporated (MPLA and QS-21; both part of GSK’s
vaccine adjuvant AS01) to determine their impact the Ag-specific CD8+ response. Generation of Ag-specific
CD44+ CD62L+ cells will be assessed to determine whether such central memory cells are more effective in
eradicating tumors. Vaccine efficacy will be tested in multiple prophylactic and therapeutic local and metastasis
tumor models. Therapeutic treatment of large tumors will be assessed with the impact of cyclophosphamide and
checkpoint blockade. Mechanistic insights will be probed by assessing how the delivered peptide reaches MHC-
I. It is hypothesized that his-tag peptides bind to CoPoP liposomes, and undergo serum-stable transit to draining
lymph nodes. There, they are phagocytosed by dendritic cells where the reductive environment of phagosomes
is also suspected to induce the release of the peptide from the CoPoP liposomes. Toll-like receptor in the bilayer
are hypothesized to upregulate the expression of MHC-I within the phagosome. Further studies will assess the
viability of SNAP immunization and antigen multiplexing as an in vivo screening tool for peptide microlibraries
using established tumor-associated antigens and neoantigens that will be identified with next-generation
sequencing. Finally, the safety and...

## Key facts

- **NIH application ID:** 10320831
- **Project number:** 5R01CA247771-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Scott I. Abrams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,870
- **Award type:** 5
- **Project period:** 2020-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320831

## Citation

> US National Institutes of Health, RePORTER application 10320831, A Cobalt Porphyrin Nanoliposome Adjuvant for MHC-I-Restricted Cancer Peptide Vaccines (5R01CA247771-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10320831. Licensed CC0.

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