The landscape of genomic variants in the allogeneic cellular cancer vaccine VACCIMEL

CARRI, IBEL; SCHWAB, ERIKA; BARRIO, MARÍA MARCELA; MORDOH, JOSÉ; NIELSEN, MORTEN

Simposio; 8vo Simposio Argentino de Jóvenes Investigadores en Bioinformática; 2023

VACCIMEL/CSF-470 is a therapeutic cancer vaccine that demonstrated a significant benefit in distant metastasis-free survival of cutaneous melanoma patients. VACCIMEL is composed of allogeneic human cell lines derived from four melanoma patients that were rationally selected to cover different common antigens associated with melanoma. However, other vaccine antigens that can be generated by mutations in cancer and human polymorphisms are still unknown. The purpose of this study was to detect and characterize genomic variants in VACCIMEL which can be the source of novel immunogens.To this aim, we performed whole exome sequencing of the vaccine cell lines and paired tumor/normal samples from four vaccinated patients. To identify somatic mutations in the vaccinated patient’s tumors, we followed GATK best practices and used MuTect2, a bioinformatic tool developed to compare normal and tumor samples. A similar procedure was performed to compare the exomes of the cell lines to the normal exomes of the vaccinated patients. Variants were annotated with Variant Effect Predictor (VEP) with complementary information from the Catalogue of Somatic Mutations in Cancer (COSMIC) and the Database of Single Nucleotide Polymorphisms (dbSNP). Also, the variants were contrasted with the somatic mutations of the vaccinated patients using bcftools, and with other melanoma patients from The Cancer Genome Atlas (TCGA).The average of non synonymous coding variants of the vaccine, when compared with the patients’ germinal data, was approximately 10000. Of these total variants, 62% were found in COSMIC and 15% were known human variants reported in dbSNP. Regarding melanoma patients, the vaccinated patients’ tumors shared 5, 11, 2120 and 24 variants with the vaccine, respectively and from 269 melanoma tumors in TCGA, 189 have variants shared with the vaccine cells.A novel approach to identify variants in allogeneic cell lines was successfully applied. This allowed us to identify that the majority of the vaccine exomic variants are reported in COSMIC, and therefore, are related to cancer. Also we could validate that most melanoma tumors share variants with the vaccine. These variants may generate targets of a therapeutic antitumor immune response.