a novel cancer vaccine strategy based on hla-a0201 matched allogeneic plasmacytoid dendritic cells新型癌症疫苗的策略基于hla-a0201匹配同种异体血浆树突细胞.pdfVIP

A Novel Cancer Vaccine Strategy Based on HLA-A*0201 Matched Allogeneic Plasmacytoid Dendritic Cells Caroline Aspord1,2,3*, Julie Charles1,2,3,4, Marie-Therese Leccia2,3,4, David Laurin1,2,3, Marie-Jeanne Richard2,3,5, Laurence Chaperot1,2,3, Joel Plumas1,2,3* 1 Etablissement Franc¸ais du Sang Rhone-Alpes, RD Laboratory, La Tronche, France, 2 University Joseph Fourier, Grenoble, France, 3 INSERM, U823, Immunobiology Immunotherapy of Cancers, La Tronche, France, 4 Centre Hospitalier Universitaire Grenoble, Michallon Hospital, Dermatology, pole pluridisciplinaire de medecine, Grenoble, France, 5 Centre Hospitalier Universitaire Grenoble, Michallon Hospital, Cancerology and Biotherapy, Grenoble, France Abstract Background: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs) in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. Methods and Findings: Stimulation of PBMC from HLA-A*0201+ donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% + tetramer CD8 T cells). The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients’ own autologous melanoma tumor cells. This semi-allogeneic pDC vac