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710 Case report and proof of concept: use of dendritic cells pulsed with tumor neoantigens for immunotherapy of patients with persistent triple-negative-breast-cancer after neoadjuvant chemotherapy
<h3>Background</h3> Triple negative breast cancer (TNBC) is a tumor with a poor prognosis due to the lack of therapeutic alternatives. Neoadjuvant chemotherapy with Doxorubicin-Cyclophosphamide (NAC-AC) and surgery is frequently used for the management of this tumor, however, after two to three years of treatment, a significant percentage of patients with remaining tumor after NAC-AC, experience a relapse responsible for high morbidity and mortality. Although recent studies have suggested that personalized cancer vaccines based on tumor-specific neoantigens could be a promising therapy for several solid tumors, their utility for immunotherapy of patients with TNBC is lacking. <h3>Methods</h3> A TNBC patient with remaining tumor after NAC-AC was vaccinated with six doses of dendritic cells pulsed with a neoantigen selected based on the profile of tumor mutations expressed before and after NAC-AC. Multiparametric flow cytometry and IFN-y-ELISPOT were used to monitor for one year the response of CD8+ T Lymphocytes (LT-CD8+) specific for neoantigens expressed by the tumor before and after NAC-AC and surgery. <h3>Results</h3> Our results show that neoantigen-specific LT-CD8+ were present in the blood before vaccination and that neoantigen recognition by these lymphocytes - evidenced by the secretion of IFN-y and the expression of the activation markers CD69 and CD154 - was the highest after the sixth dose of the vaccine. On the other hand, the analysis of the TCR repertoire of LT-CD8+ present in blood after stimulation with the neoantigen<i> in vitro</i> allowed us to establish the identity of CDR3-TCRs specific for the neoantigen. Interestingly, after vaccination the expansion of LT-CD8+ specific for a new neoantigen not included in the vaccine was detected. <h3>Conclusions</h3> Taken together, our results suggest that the use of personalized vaccines based on dendritic cells pulsed with tumor neoantigens may be useful for immunotherapy of TNBC patients with remaining tumor after NAC-AC. <h3>Acknowledgements</h3> The authors express their gratitude to the volunteer who generously participated in the study which made this research possible. This study was supported by funding from Vicerrectoria de Investigación of the Universidad Nacional de Colombia (Hermes 57647, 57457 and 56075) and Grants from MinCiencias (920 grant, RC 800-2023 and 841 grant, RC 903-2019). <h3>Trial Registration</h3> Patient FMR participated in the Clinical Trial: 'Phase I clinical study of immunotherapy with personalized synthetic vaccines in patients with triple negative breast cancer', (ClinicalTrials: NCT04105582). <h3>Ethics Approval</h3> The ClinicalTrials: NCT04105582 was approved by the Ethical Committee, Universidad del Rosario Ethical Committe. Study DVO005 1098-CV1154. March 19 – 2020.
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Immunotherapy and Immune Responses
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FuenteRegular and Young Investigator Award Abstracts