Abstract P4-14-11: Prolonged survival of mice bearing HER2 positive breast cancer with a therapeutic cancer vaccine via intra-reconstructed abdominal flap administration
Authors: Xiaoling Liu, Junhua Mai, Chaoyang Meng, Wei Wei, Haifa Shen
Journal: Cancer Research (2020)

Abstract Background: Previously we reported a porous silicon micro-particle based cancer vaccine, which stimulated robust CD8+ T cell-dependent anti-tumor immunity in mice bearing HER2-positive breast cancer. In this study we evaluated the efficacy of the vaccine via single injection into reconstructed abdominal flap after primary tumor mastectomy. Method: To generate murine model of HER2 positive breast cancer murine, 1 × 105 TUBO/luciferase cells were injectedinto both mammary gland fat pad and left ventricle of each 6-8 weeks old female Balb/c mice. Primary and systemic metastatic tumor growth were monitored with a IVIS-200 imaging system. Four days after tumor inoculation, mammary gland fat pad with primary tumor was resected by mastectomy, and superficial inferior epigastric(SIE) vessels based abdominal flap was used for abdominal reconstruction. During the surgery, mice also received one of the three treatments below: 1) negative control without treatments; 2) single intra-flap vaccination of cancer vaccine; and 3) single injection of cancer vaccine via footpad injection. Therapeutic efficacy were monitored with IVIS system weekly. To analyze immune response, popliteal and inguinal lymph nodes were collected one day and seven days post vaccination, and activation of dendritic cells and T cells was evaluated with a flow cytometry. HER2 specific T cells in splenocytes which highly expressed interferon-gamma (IFNγ) were counted by ELISpot. CD3+ T cell infiltration in brain metastatic nodules were analyzed by immunohistochemical assay. Result: Prolonged survival of mice bearing HER2-positive breast cancer was achieved by both intra-flap and intra-dermal vaccination of cancer vaccine. Mice vaccinated via intra-flap injection extended median survival by 9 days (p=0.025), although not as long as intra-dermal treatment (15 days, p=0.034), comparing to control group. In lymph nodes, activated dendritic cells increased in both two vaccinated groups. Interestingly, intra-flap vaccination induced higher response in inguinal lymph node, which considered as the major draining lymph node of this route. Meanwhile, intra-dermal vaccination raised higher immune response in popliteal lymph node. In ELISpot assay, IFNγ secreted T cells were found abundant in splenocytes from both two vaccination groups. Furthermore, efficient infiltration of T cells inside the brain metastatic nodules was found in intra-dermal injection group, which provided potential protection from distal recurrence after mastectomy. Conclusion: Cancer vaccine administrated via intra-flap injection effectively stimulated systemic immune response, and slowed down tumor progression in murine HER2 positive breast cancer model. Citation Format: Xiaoling Liu, Junhua Mai, Chaoyang Meng, Wei Wei, Haifa Shen. Prolonged survival of mice bearing HER2 positive breast cancer with a therapeutic cancer vaccine via intra-reconstructed abdominal flap administration [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 P4-14-11.