Data from Neoadjuvant Endocrine Treatment plus Mammaglobin-A DNA Vaccine Induces Antitumor Immune Responses in the Primary Tumor and Peripheral Blood of Patients with Breast Cancer: Insights from a Phase Ib Clinical Trial
Year: 2026
Type: other
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 patients with breast cancer. 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 Ib clinical trial in patients with estrogen receptor–positive breast cancer 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 enzyme-linked immunospot (ELISpot) analysis of peripheral blood mononuclear cells demonstrated that Mam-A vaccination induced Mam-A–specific T cells in 8 of 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 metaclusters 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, postvaccination 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.
Authors: Rashmi Mishra, Foluso Ademuyiwa, Yilin Yang, John Herndon, Lijin Li, Cherease Street, Nancy Myers, Ina Chen, Xiuli Zhang, Ian S. Hagemann, Feng Gao, Christopher A. Miller, Narendra V. Sankpal, Joel M. Guthridge, Madelyn Carmody, Cynthia X. Ma, Rama Suresh, Timothy P. Fleming, Caleb Marlin, S. Peter Goedegebuure, William E. Gillanders
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W7147739070