Induction of immune responses and clinical efficacy in a pilot personalized trial of 26 multi-epitope immunotherapy using long peptides Th1 and CD8 simultaneously in progressive tumors

Autor: Juan P Marquez-Manriquez, JOSE ANTONIO MATUTE-BRISENO, SALVADOR ICEDO-ZAMORA, ALBERTO DURAZO-ACUNA, PEDRO ALEJANDRO Alejandro Lucero-Diaz, MARTIN ORLANDO ROSAS-DELGADO, ALEJANDRO CAMACHO-HERNANDEZ
Rok vydání: 2019
Předmět:
Zdroj: The Journal of Immunology. 202:70.17-70.17
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.202.supp.70.17
Popis: Background Most of the immunotherapy trials in progressive cancer are limited targeting few antigens and most of them are not clinically relevant as they are not important for tumor survival. For such reason our approach is to develop multi peptide immunotherapy in order to potentially avoid chemoresistance and target simultaneously several biologically relevant pathways. We treated patients with progressive cancer after failure of the standard of care treatment with this methodology. Methods N=12 patients with progressive tumors such as pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), epithelial ovarian cancer (EOC) and sarcomas (ES) were treated with 26 long-peptides for 3 months until progressive disease. The patients were analyzed initially for several immune parameters such as DTH in both tumor area and non-tumor area, Granzyme B ELISPOT, Antigen-specific ELISA, T-cell expansion using individual peptides and immunohistochemistry. Results We were able to improve significant the mOS (38 months) with absence of toxicity. The proteins that we targeted were previously showed that were biologically relevant according with the siRNA studies we were able to silence and kill permanently in vitro different chemoresistant cell lines from the types of tumors treated as following PDAC (n=0.001), CRC (n=p0.005), EOC (P=0.001) and sarcomas (n=0.0001). Discussion After we validate this data with a large cohort of progressive tumors we will be able to prepare a clinical trial phase/II I order to accelerate the potential addition of these type of antigen active specific immunotherapy with other treatment modalities such as immunogenic chemotherapy, cytotoxic chemotherapy, radiotherapy, etc.
Databáze: OpenAIRE
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