一种临床采用的疫苗平台与新的免疫原性表位联合对抗前列腺癌

Introduction: Prostate cancer (PCa) is the archetype of an immunological “cold” tumour, characterised by a very low mutational burden and neoantigen presentation, and minimal immune infiltration. In line with this, immune therapies turn out to be ineffective in PCa. The project aims at transforming PCa into an immunocompetent tumour through the development of ad hoc vaccinal strategies. Methods and Results: Recruiting adaptive immune cells into the prostate gland: The efficacy of a versatile clinical-adopted vaccine platform (X) to attract the immune system into the prostate tumour is under study in mouse model of advanced PCa. Immunohistochemistry on formalin-fixed paraffin-embedded (FFPE) slides of PCa allografts is defining the tumour microenvironment (TME) composition. Cd8 + T-cells infiltrate PCa tumours, while Cd4 + T-cells and FoxP3 + regulatory T-cells preferentially accumulate in the periphery. A dense network of Collagen VI fibrils might be responsible for the different distribution. Intratumoral injection of X adjuvants does not change T cells behaviour, but it stimulates the formation of tumour abscesses surrounded by tightly packed neutrophils. Identifying immunogenic antigens to instruct effector T cells against PCa: Non-canonical human leukocyte antigen (HLA)-restricted PCa antigens are caught among peptides coming from aberrant splicing events, expression of transposable elements and atypical expression of tissue/development-restricted genes thanks to the integration of in-depth RNA Seq transcriptome with mass spectrometry HLA-I epitome analyses. Conclusions: We expect that the ability to attract the immune system into the prostate combined with the identification of immunogenic epitopes, will pave the way for the development of tailored and affordable vaccine therapies for the effective treatment of advanced PCa.