Celloram, a Cleveland-based biotech firm, is testing a cancer vaccine that taps into the immune memory many people gained from COVID-19 exposure or vaccination. The approach seeks to harness that pre-existing immunity in order to boost the body’s ability to fight tumors.
Design that borrows SARS-CoV-2 immunity
The preclinical study, released in Nature Communications, describes a dendritic-cell platform named Protexi. Researchers loaded the cells with short fragments of the SARS-CoV-2 Spike protein to activate CD4 T cells alongside the cytotoxic response aimed at tumor antigens. This dual activation strategy is intended to create a more robust and coordinated immune attack.
Dendritic-cell vaccines normally aim to prime cytotoxic T cells, yet only about 15% of patients achieve a measurable tumor response. By adding a well-known helper epitope, the team hopes to improve that figure. The inclusion of the Spike-derived helper fragment is meant to recruit additional immune support that is often missing in standard formulations.
In mouse experiments, animals receiving Protexi survived to day 40 at a rate of 100%, while those given a conventional dendritic-cell vaccine showed a 40% survival rate. A melanoma model reported that five of seven mice had tumors smaller than 200 cubic millimeters by day 26. These results suggest a notable advantage for the Spike-enhanced design.
Why COVID-19 memory matters
The authors note that over 80% of the U.S. population and about 65% of people worldwide have received at least one COVID-19 vaccine dose, and many unvaccinated individuals possess natural-infection memory. This widespread exposure creates a large pool of potential helper-cell donors for the vaccine.
“Spike-specific CD4⁺ T-cell memory is broadly durable across the population that’s been vaccinated or infected. Indeed, this is the whole premise the platform depends on,” said John Letterio, a co-author of the paper.
Letterio added that studies show CD4 T cell responses to COVID are durable for up to 2 to 4 years in vaccinated patients, while viral CD4 T cell memory for SARS-CoV-1 could be retained for up to 17 years. These timeframes underline the long-lasting nature of the targeted immune component.
Should a patient’s existing immunity prove insufficient, the researchers demonstrated a “priming” dose of dendritic cells loaded with Spike and ovalbumin—an egg protein used as a stand-in—restored a strong CD4 T-cell response even without pre-existing immunity, Letterio said.
Earlier work from the 1990s established that CD4 T helper cells are required for optimal CD8 induction against MHC-II-negative tumors. More recent research has shown that tumor rejection during immunotherapy requires both CD4 and CD8 tumor-specific T cells, he said.
Identifying potent CD4 epitopes is computationally difficult, which has limited their inclusion in vaccine designs. By selecting the Spike protein, one of the most thoroughly mapped antigens, the team sidestepped that bottleneck.
“Any CD4 T-cell epitope that a patient already has strong, durable memory against should, in principle, be able to serve the same helper function,” Letterio said.
Celloram now aims to file an IND with the FDA and launch a first-in-human trial targeting sarcoma patients at the Angie Fowler Adolescent & Young Adult Cancer Institute.
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