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Soo Park, MD
Soo Park, MD
Posted: Tuesday, July 9, 2024
For patients with Merkel cell carcinoma, tumor growth may be suppressed by therapeutic vaccination with large T antigen (LTA)-targeting mRNA, according to a preclinical study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 2637). Alexander Frey, MD, of Yale School of Medicine, New Haven, Connecticut, and colleagues believe this vaccine may ultimately be of benefit in this type of skin cancer through an increase in LTA-specific CD8-positive T cells, interferon-gamma release, and Merkel cell carcinoma–specific killing.
In vivo models of Merkel cell carcinoma were established using B16-F10 murine models that expressed a truncated LTA oncoprotein. Optimized mRNA coding was created using in vitro transcription. Tumor cells that expressed LTA were subcutaneously injected into mice. The mice were treated with LTA mRNA or a placebo with or without the addition of anti–PD-1 antibodies. In addition, a separate cohort of mice received three doses of the LTA mRNA or placebo before injection with tumor cells.
The study authors reported an increased extent of tumor growth suppression observed with LTA mRNA treatment (mean volume = 47.3 mm3) compared with placebo (mean volume = 575.1 mm3). Similarly, treatment with LTA mRNA resulted in a prolonged median survival (46 days) compared with placebo (24 days). Furthermore, the combination of LTA mRNA plus anti–PD-1 treatment resulted in 100% tumor regression compared with placebo alone (0% regression) or anti–PD-1 alone (50% regression). Treatment with LTA mRNA led to an increase in CD3-positive and CD8-positive cells compared with placebo. Moreover, peripheral blood mononuclear cells vaccinated with LTA mRNA led to the observed rise in the LTA tetramer–specific CD8-positive T cells.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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