Effect of subcutaneous multi-peptide active antigen-specific immunotherapy at lymph nodes and tumor sites on clinical outcomes in progressive tumors.

Juan Pablo Marquez-Manriquez CICS USA, Seattle, WA info_outline Juan Pablo Marquez-Manriquez, Pedro Alejandro Lucero-Diaz, Jose Antonio Matute-Briseno, Alejandro Camacho-Hernandez, Dolores Gallardo-Rincon

Authors Juan Pablo Marquez-Manriquez CICS USA, Seattle, WA info_outline Juan Pablo Marquez-Manriquez, Pedro Alejandro Lucero-Diaz, Jose Antonio Matute-Briseno, Alejandro Camacho-Hernandez, Dolores Gallardo-Rincon Organizations CICS USA, Seattle, WA, Centro de Investigacion de Cancer en Sonora Campus Ciudad Obregon, Sonora, Ciudad Obregon, Mexico, Sonora Cancer Research Center (CICS USA), Lynnwood, WA, Centro de Investigacion de Cancer en Sonora Campus Ciudad Obregon, Sonora, Ciudad Obregon, SO, Mexico, Department of Medical Oncology, Ovarian Cancer Program, Instituto Nacional de Cancerología, Mexico City, DF, Mexico Abstract Disclosures Research Funding Other Foundation Background: The tumor and lymph nodes (LN) microenvironment clinically speaking are mainly unexplored and there are limited clinical studies of immunotherapeutic approaches manipulating those in progressive cancer patients. The tumor and LN microenvironment offers an opportunity to treat locally with multi-peptide immunotherapy in challenging clinical situations where we can have still a potential safe and effective therapeutic approach using the concept treat locally treat systemically. Methods: N = 11 patients were enrolled after the local IRB ethic committee approved the pilot clinical study number CICS/SS/0035. Previous identified targets such as FAP, b-2-microglobulin, Fascin, RCAS1/EBAG9, Bcl-2, survivin, Sox2, Ape-1, Valosin containing-protein (VCP) and EGFR were analyzed by IHC, Th1 and CD8 long-peptides were predicted, immune assays using PBMCs including tumor microenvironment were performed to detect Granzyme B by ELISPOT, naturally processed epitopes by T-cell expansion and cytokines. Patients were treated subcutaneously (S.C.) eight times in the axillary and inguinal LN area one week apart. Afterwards we treated S.C. as well but now in the areas with tumor activity according with the CT or PET every week 10 times. Initial DTH and at the end of the treatment was performed. Pathological, clinical and immunological correlations were made using multivariate analysis. Results: Despite progressive disease 100% of the patients responded to the treatment. 80% had CR and 20% pseudo-progression and then CR. 100% of the patients increased the levels of Granzyme B against Bcl-2 (p = 0.001), VCP (p = 0.0001), Ape-1 (p = 0.005) and RCAS1 (P = 0.0001) and this correlated with the scans post-treatment. The patients showed more CD8 infiltration in the DTH test at the tumor site (p = 0.002) than in the non-tumor site (p = 0.01). The number of metastatic lesions in lungs (p = 0.004) and hepatic tissue (p = 0.001) disappeared and correlated with increased levels of IL-12 production in vivo . Conclusions: Treating immunologically the LN and the microenvironment of the areas with tumor activity is a feasible and safe approach to limit systemic toxicity and improve the clinical outcomes in patients with progressive cancer including bone sarcoma, epithelial ovarian cancer, PDAC, pediatric sarcomas and TNBC.