Abstract P5-04-10: Immune and transcriptional signatures of dendritic cell (DC) vaccination combined with chemotherapy in locally advanced, triple-negative breast cancer (TNBC) patients
Authors: Te-Chia Wu, Joyce O’Shaughnessy, Lee K. Roberts, Jennifer L. Smith, Susan B. Burkeholder, Jennifer Finholt, Jessica Tarnowski, Tuoc Dao, Jeffrey Lamont, Sandra M. Zurawski, Phuong Nguyen, Yuanyuan Wang, Kyung In Kim, Derek Blankenship, Jacob Turner, Xuan Wang, Florentina Marches, Maren K. Levin, Michael Grant, Gerard Zurawski, Virginia Pascual, Jacques Banchereau, Karolina Palucka
Journal: Cancer Research (2020)

Abstract Women with triple-negative breast cancer (TNBC) have an increased pathologic complete response rate (pCR; residual disease after neoadjuvant chemotherapy) as compared to women with non-TNBC, and those with pCR have a 90% disease-free survival. However, women with TNBC who do not achieve a pCR have an increased risk of recurrence, decreased overall survival, and post-recurrence survival as compared to women with non-TNBC who do not achieve a pCR. A high priority for clinical research is therefore to increase the pCR rate in breast and axilla with preoperative therapy, as therapeutic options for patients who do not have a pCR are limited. Immunotherapy is an attractive strategy as human BCs can be immunogenic and enhancing the immune effector function may augment the cytotoxic effects of standard therapies. Immunity against tumor antigens can be boosted in cancer patients by vaccination with ex vivo-generated tumor antigen-loaded DCs. Here, we report the extended analysis of a clinical trial on 10 TNBC pts assessing the feasibility of combining cyclin B1/WT1/CEF (antigen)-loaded DC vaccination with preoperative chemotherapy in patients with locally advanced TNBC. Combination of preoperative chemotherapy and intratumoral and subcutaneous autologous DC vaccination led to 70% of combined rate of pCR and residual cancer burden 1 (RCB1). To assess expansion of antigen-specific T cell responses, IFN-g-ELISpot was carried out with PBMCs from baseline (BL) and several time points during vaccine treatment that were cultured with control peptides or with peptide libraries covering vaccine antigens. The expansion of antigen-specific immune responses could be detected at various time points post treatment. Transciptional profiling on blood (Nanostring) and tumors (RNAseq) revealed profound changes in immune transcription signatures. T cell and DC signatures in blood and T cell, inflammation, cytotoxic and cell cycle signatures in pre-chemotherapy breast cancer biopsies were linked with pathological responses in definitive surgery specimens. Taken together, differential gene and immunologic signatures of the pre-treatment breast cancer biopsies distinguish pts who have a pCR vs no pCR and can identify potential therapeutic targets for pts with TNBC. Citation Format: Te-Chia Wu, Joyce O’Shaughnessy, Lee K. Roberts, Jennifer L. Smith, Susan B. Burkeholder, Jennifer Finholt, Jessica Tarnowski, Tuoc Dao, Jeffrey Lamont, Sandra M. Zurawski, Phuong Nguyen, Yuanyuan Wang, Kyung In Kim, Derek Blankenship, Jacob Turner, Xuan Wang, Florentina Marches, Maren K. Levin, Michael Grant, Gerard Zurawski, Virginia Pascual, Jacques Banchereau, Karolina Palucka. Immune and transcriptional signatures of dendritic cell (DC) vaccination combined with chemotherapy in locally advanced, triple-negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-10.