Abstract Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This profile limits treatment options primarily to chemotherapy, which is often associated with drug resistance, poor clinical outcomes, and is further challenged by the intrinsic heterogeneity and immunosuppressive tumor microenvironment of TNBC. JX-594 (pexastimogene devacirepvec; Pexa-Vec®), an oncolytic vaccinia virus derived from the Wyeth vaccine strain, has demonstrated multiple antitumor mechanisms, including direct oncolysis, immune activation, and disruption of tumor vasculature. Patient-derived xenograft (PDX) models closely replicate the original human tumors, providing a clinically relevant platform for evaluating novel therapeutics such as JX-594. In this study, we investigated the antitumor efficacy of intratumoral JX-594 administration in TNBC PDX models and assessed its effects on tumor cell proliferation, angiogenesis, and viral replication. Methods: Patient-derived xenograft (PDX) models were established by implanting fresh tumor tissues from two TNBC patients (ages 54 and 55) into the mammary fat pads of female NOD/SCID mice. Tumors were serially passaged and confirmed to retain human origin via Short Tandem Repeat (STR) profiling. Once tumors reached approximately 30 mm3 in volume, mice were randomized into two groups (n=6 per group per model): control or JX-594 treatment. JX-594 (1×107 PFU in 50 µL saline) was administered intratumorally once weekly for four weeks. Tumor size, body weight, and general health were monitored. On day 28, mice were sacrificed, and tumors were collected, formalin-fixed, and paraffin-embedded for hematoxylin and eosin (H 0.01). Importantly, oncolytic virotherapy was well tolerated, with no evidence of systemic toxicity or weight loss in treated mice. IHC analysis revealed extensive tumor cell death in JX-594-treated TNBC PDX models, as indicated by markedly reduced Ki-67 proliferation index and CD31 vascular marker expression levels. The presence of vaccinia antigen confirmed active viral replication within tumors. Conversely, control groups showed higher Ki-67 and CD31 expressions. Conclusion: This study demonstrates that intratumoral administration of the oncolytic vaccinia virus JX-594 effectively suppresses tumor growth in PDX models of TNBC. JX-594 induces tumor cell death, inhibits proliferation, and disrupts tumor vasculature, collectively contributing to its potential antitumor activity. These findings support the potential of JX-594 as a promising therapeutic strategy for treatment of TNBC. Citation Format: J. Lee, Y. Kim, Y. Cha, N. Lee, K. Oh, J. Jeong, J. Kim. Antitumor activity of the oncolytic virus JX-594 in patient-derived xenograft models of triple-negative breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-13-06.
Lee et al. (Tue,) studied this question.