A Cleveland-based biotech company, Celloram, is developing a cancer vaccine that utilizes the immune memory of COVID-19 to activate T cells against tumors in mice. The company, in partnership with Case Western Reserve University and University Hospitals Cleveland Medical Center, has published preclinical results for the new dendritic cell vaccine, called Protexi, in Nature Communications.
Protexi uses epitopes derived from the Spike protein of SARS-CoV-2 to activate CD4 T cells, in addition to CD8 cells. This approach could make the vaccine more effective than activating CD8 alone, as CD4 cells help draw CD8 cells to the tumor and give dendritic cells the signal they need to fully activate them.
Preclinical Results
In one experiment, mice that received CD4 cells engineered to recognize the target showed 100% survival to day 40, compared to 40% for a conventional dendritic cell vaccine in mice. A melanoma model also showed promising results, with five of seven mice having tumors measuring under 200 cubic millimeters on day 26.
Celloram’s researchers believe that the immune memory of COVID-19, which is present in over 80% of the U.S. population and 65% of the global population, can be leveraged to activate CD4 T cells and enhance the effectiveness of the vaccine.
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Mechanism and Potential
John Letterio, a co-author on the paper, notes that “Spike-specific CD4⁺ T-cell memory is broadly durable across the population that’s been vaccinated or infected.” This durability is key to the platform’s potential, as it allows for the activation of CD4 T cells and the enhancement of the vaccine’s effectiveness.
The team chose to use the SARS-CoV-2 Spike protein because its CD4 T cell antigen has been extensively mapped, and a large proportion of the global population carries the immune memory. However, the mechanism could work with other epitopes, as any CD4 T-cell epitope that a patient already has strong, durable memory against should be able to serve the same helper function.
They are now working to advance Protexi toward IND submission to the FDA and a first-in-human clinical trial in patients with sarcoma at the Angie Fowler Adolescent & Young Adult Cancer Institute. If successful, this approach could provide a new and effective way to harness the immune system to fight cancer.
