Cancer Immunol Res. 2026 Feb 6. doi: 10.1158/2326-6066.CIR-25-0666. Online ahead of print.
ABSTRACT
Tumor-associated antigen (TAA) vaccines are being explored as a strategy to induce antitumor immune responses. Mammaglobin-A (Mam-A) is a TAA expressed in >50% of breast cancer (BC) patients. Previously, we have shown that Mam-A DNA vaccines induce antitumor immune responses in patients with stable metastatic disease. To further evaluate the potential of the Mam-A vaccine, we initiated a phase-1b clinical trial in estrogen receptor-positive BC patients prior to surgery. Eight patients were assigned to Arm 1 (neoadjuvant endocrine therapy alone) and 17 to Arm 2 (neoadjuvant endocrine therapy plus Mam-A vaccination); the final analysis included 8 patients from Arm 1 and 13 from Arm 2. Ex vivo ELISpot analysis of peripheral blood mononuclear cells demonstrated that Mam-A vaccination induced Mam-A-specific T cells in 8/13 patients. Intracellular cytokine staining, and Mam-A-specific tetramer staining revealed that vaccine-induced Mam-A-specific T cells included both CD4+ and CD8+ polyfunctional T cells. Finally, high-throughput imaging mass cytometry identified 24 cellular meta-clusters with features of tumor, immune, stromal, and endothelial cells and revealed an increased CD8+ T-cell prevalence in the tumor after Mam-A vaccination. In particular, vaccination was associated with the infiltration of PD-1+CD8+ T cells. In addition, post-vaccination tumor samples exhibited close spatial interactions between cytotoxic CD8+ T cells (CTL) and Mam-A+ tumor cells and between CTL and antigen-experienced CD4+ T cells. Together, these results suggest that Mam-A DNA vaccination elicits both systemic and intratumoral antitumor immune responses.
PMID:41650206 | DOI:10.1158/2326-6066.CIR-25-0666