Precision DC: Personalized neoantigen dendritic cell vaccine pilot trial for high-risk triple-negative breast cancer after neoadjuvant therapy.

TPS643 Background: Treatment for stage II-III triple negative breast cancer (TNBC) uses neoadjuvant chemoimmunotherapy (NCT) with the goal of achieving pathologic complete responses. TNBC patients with significant residual cancer burdens (RCB II/III) after NCT have a high risk of early relapse/death despite use of adjuvant therapies like capecitabine. Moffitt Cancer Center's breast program uses a highly immunogenic dendritic cell vaccine platform (DC1) against HER2 overexpressing tumors in previous studies demonstrating anti-tumor efficacy (Han, JAMA Onc 2025). TNBC often has multiple somatic mutations leading to expression of altered immunogenic proteins known as neoantigens. We hypothesize that the residual primary TNBC after NCT can be sequenced to identify the most immunogenic neoantigens and include them as targets in an adjuvant DC1 vaccine to stimulate cytotoxic T cell responses that eliminate residual micrometastatic disease. The PRECISION DC trial was initiated to study the feasibility of adjuvant neoantigen DC1 vaccines for high risk TNBC. Correlatives include immune response to neoantigens using ELISPOT and immunopeptidomics to study processing of peptides by the dendritic cells (NCT06435351). Methods: PRECISION DC is a single-arm pilot study open at the Moffitt Cancer Center enrolling stage II-III TNBC patients with RCB II/III disease and who are within 18 months of their last dose of KEYNOTE-522 chemotherapy without known metastatic disease. Eligible patients will have their residual tumor tissue whole exome sequenced, and mutated 25 mer long peptides are analyzed using a modified NetMHCII pipeline to rank these mutations based on a combined score representing multiple factors including expression, predicted MHC binding, and agretopicity. The top ten scoring peptides that also pass a peptide synthesis screen for excessive hydrophobicity are selected for inclusion in each patient’s personalized DC1 vaccine. The relevant peptides for each patient are used to stimulate pheresed autologous dendritic cells ex-vivo. Moffitt’s GMP cell therapy facility creates cryopreserved aliquots of 50 million cells to create DC1 vaccine doses. Patients get three intranodal DC1 inguinal injections q2weeks under ultrasound guidance in the priming phase and then two booster shots at 6 and 12 months either before or after adjuvant capecitabine (if given) per treating physician guidance. PRECISION DC opened 10/2024 and accrual to date is 22/26 planned patients with 4 remaining patients already identified. Primary endpoint is feasibility (% pts with successful vaccine administration w/ goal > 60%); secondary endpoints include safety, immune responses, and 5-year disease-free outcomes. If successful, PRECISION DC will set the stage for a prospective randomized trial of personalized autologous DC1 neoantigen vaccines to prevent recurrence of residual TNBC following NCT. Clinical trial information: NCT06435351 .