Juan Pablo Marquez-Manriquez
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Alejandro Camacho-Hernandez
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Pedro Alejandro Lucero-Diaz
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Dolores Gallardo-Rincon
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Martin Orlando Rosas-Delgado
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e15268 Background: Typically cancer vaccines for relapse prevention in epithelial ovarian cancer (EOC) are administrated in distant anatomical sites away from the primary tumor location. Ideally for EOC relapse prevention vaccines we should explore different anatomical sites related with the original tumor location and nearby lymph nodes, in order to observe if the administration would have better clinical impact due to a potential access to the tumor microenvironment. Moreover most trials for EOC relapse prevention use one or few targets and is mainly unknown if they are relevant to promote EOC relapse. We treated EOC patients with a multi-peptide vaccine administered in lymph nodes (LN) and in the peritoneum area and were able to suppress cancer relapse with not significant adverse effects after eight years. Methods: We enrolled n = 25 EOC patients in our study and identified by systematic review and validated by siRNA six proteins involved in EOC relapse and fourteen peptides were predicted. Twelve peptides were immunogenic by Granzyme B ELISPOT, DTH and ELISA. Patients were immunized with the vaccine in axillary and inguinal LN subcutaneously every week for four weeks, every two-weeks four times and finally every month for a total of thirty-six months. Clinical and laboratory evaluations were performed every 2-months and at the end of the study. Results: 100% of the patients developed both antibodies against all the peptides by ELISA and CD8 specific cells. The peptides of the six proteins were able to induce T cell expansion in both peptides and purified protein (p = 0.0001) and (p = 0.05), respectively for Ape-1. The selected targets were all able to induce DTH and ELISA responses with statistical significance. Peptides predicted from Bcl-2, survivin, Ape-1, Sox2, EGFR and RCAS1/EBAG9 were able to increase and sustain the levels of Granzyme B ELISPOT. Bcl-2 A peptide (p = 0.001), Bcl-2 B (p = 0.005), Bcl-2 C (p.0002), survivin A (p = 0.001), Survivin C (0.05), Ape-1 A (0.0001), Ape-1 D (p = 0.001), Sox2 A (p = 0.003), Sox2 B (p = 0.0001), EGFR B (p = 0.0001) and EGFR D (p = 0.001). Conclusions: Treating EOC patients in remission in zones hardly explored previously in order to potentially improve the activation of antigen-specific Th1 and CD8 cells with specific peptides seems promising as a feasible and safe approach to prevent EOC relapse.
708 Preclinical studies support therapeutic application of the leukaemic cell-based cancer relapse vaccine DCP-001 in ovarian cancer