PCV R&D

PROFILE

Cancer arises from the accumulation of genetic mutations. TMB, a measurement of such mutations carried by cancer cells, is reported as the number of mutations in a specific area of genetic material. High TMB related to neoantigen load and presents of T cell infiltrates. Neoantigen targeted personalized cancer vaccine (PCV) can both expand pre-existing neoantigen-specific T-cell populations and induce a broader repertoire of new T-cell specificities in cancer patients, tipping the intra-tumoral balance in favor of enhanced tumor growth and invasiveness suppression. PCV may protect patients against cancer relapse, according to 2 studies published in Nature in July 2017, 12 of 19 melanoma patients in 2 clinical trials remained cancer free for up to 2 years after receiving PCV. This may be a game changer in cancer immune-therapy. However, its application still faces some challenges. Melanoma tumor cells contain more somatic mutations (high TMB), which may be more suitable for the selection of neoantigens. The preparation of PCV takes 6-12 weeks. Invasive removal of advanced tumor tissues is needed to detect and confirm somatic mutations. The accuracy of predicting neoantigens based on current bioinformatics algorithms is relatively low. To overcome these shortcomings, our company has established mouse models of lung cancer, skin cancer and liver cancer and carried out some preclinical studies. Circulating tumor cells (CTC) and ctDNA have been noninvasively isolated and enriched in the plasma of early lung cancer animals and cancer patients. Neoantigens have been identified by combining WES and RNA-seq of CTC and PBMCs. PCVs, made from selected neoantigens, are prepared to promptly stimulate the immune response of cancer patients and animal tumor models.

PROCEDURES

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