Abstract PS13-28: Pre-treating TNBC with docetaxel and il-12 enhances anti-PD1 efficacy

Abstract

Abstract Introduction: Amongst all breast cancers, Triple Negative Breast Cancer (TNBC) account for 15-20% of all the cases. TNBC affect younger patients, and is more prevalent in African-American women. The poor prognosis for this very aggressive tumor subtype is exacerbated by the lack of specific targeted therapy against the disease. Although TNBC initially respond very well to chemotherapy, paradoxically the disease-free survival is very short. It has been showed that TNBC have higher rates of CD8+ T-cells infiltration, and express high level of PD-L1. Together, these data provide a strong rationale for the combination of chemotherapy and immunotherapy to treat TNBC patients. In this study, we investigated the response to pre-priming the tumor with one round of docetaxel and IL-12, followed by anti-PD1 maintenance in mouse E0771 and 4T1 TNBC syngeneic models. We hypothesized that docetaxel will promote the release of neo-antigens, while IL-12 will activate immunity specific to these antigens and anti-PD1 therapy prevent the exhaustion of those T-cells. Materials/Methods: Mouse TNBC E0771 and 4T1 cell lines were injected in the mammary fat pad of C57BL/6, and Balb/c mice respectively. On day 1, the mice received a single dose (20mg/kg) of docetaxel and one intratumoral injection (1.25x109) of mAdv.IL-12, a replication defective adenoviral vector containing mIL-12 (mouse) cDNA under the transcriptional control of Rous sarcoma virus long terminal repeat (provided by Dr. Chen, HMRI). Anti-PD1 (InVivoMab anti-mouse PD-1 CD279) was administered 3 times a week (2 cycles) starting 5 days post docetaxel and Il-12 treatment. At the end of the study, IFN-gamma levels were measured from blood and tumor samples; tumor sizes were compared between treatment groups (Control/mAdv.IL-12/anti-PD1/and various Combination), as well as survival curves. The metastatic burden to the lungs (H&E), as well as the apoptosis in the tumor (TUNNEL) were assessed by IHC. Results: In both 4T1 and E0771 tumor models, triple combination of docetaxel + IL-12 followed by anti-PD1 significantly reduced tumor size compared to both single agents, and double combination. In the Triple Combo group, 1 mice had lung metastasis vs all of them in the other treatment groups. IHC data indicate a higher level of TILs in the treatment groups, with a statistically significant difference in the combination groups compared to single agents. There was more apoptosis in the triple combo group as indicated by TUNNEL. Conclusion:Our preliminary data strongly supports that treating TNBC models with docetaxel and mAdv.IL-12 followed by anti-PD1 significantly slows down tumor growth, and decrease lung metastasis incidence. We are actively investigating the mechanism through which the response is achieved. Citation Format: Ann Cassany Anselme, Wei Qian, Jianying Zhou, Roberto R. Rosato, Jenny C. Chang. Pre-treating TNBC with docetaxel and il-12 enhances anti-PD1 efficacy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-28.