Abstract 5660: Vaccinia virus GLV-1h153 in combination with 131I-iodine shows increased efficiency in treating triple-negative breast cancer in vivo

Abstract

Abstract BACKGROUND: Triple-negative breast cancers (TNBC) are aggressive tumors due to their inherent biology and the lack of receptors for hormonal/targeted therapy, namely estrogen, progesterone, and Her2/neu. The human sodium iodide symporter (hNIS) is a naturally occurring protein in some human breast and thyroid tissue which enables cells to concentrate iodine, including radioiodide. In this study, we investigated the therapeutic efficacy of a new oncolytic vaccinia virus, GLV-1h153 carrying the hNIS, in combination with radioiodine in a TNBC murine model. METHODS: GLV-1h153, a replication-competent vaccinia virus, was tested against the TNBC cell lines MDA-MB-231, MDA-MB-468, HCC-1937, and HCC-1143 at multiplicities of infections (MOI) of 0.1, 1.0, and 5. Cytotoxicity and viral replication were determined. Mammary fat pad tumors were generated in athymic nude mice with MDA-MB-231 cells. A subset of xenografts were infected with GLV-1h153 and ∼150 μCi of 124I-iodine was administered. Serial Focus 120 microPET were obtained for 131I dosimetry calculations. For the combination therapy study, 14 days after cell implantation, xenografts were treated with intratumoral injection of GLV-1h153 or PBS. One week after viral injection (day 21), xenografts were further randomized into 4 treatments groups: GLV-1h153 alone, GLV-1h153 and iodine (∼5 mCi of 131I), iodine alone, or PBS and followed for tumor growth. RESULTS: Greater than 90% cell kill was achieved in all cell lines within 5 days at an MOI of 5.0. GLV-1h153 replicated efficiently in all cell lines with a peak titer of 2.6 x107 viral plaque forming units per ml (>1300-fold increase from the initial viral dose) by day 4 in cell line MDA-MB-468. Only infected tumors were identified via PET scanning compared to controls. In vivo, administration of systemic radioiodine in combination with GLV-1h153 resulted in greater tumor regression, 24 mm3 compared to 146 mm3 for the viral-treated group only (p<0.05; days 21-40), a six-fold difference. CONCLUSION: GLV-1h153 infected, replicated in, and killed all TNBC cell lines effectively. This study is the first to our knowledege to demonstrate killing of TNBC by a novel vaccinia virus in combination with radioactive 131I-iodine in an in vivo xenograft model. Our results suggest that GLV-1h153 is a promising therapeutic agent in combination with 131I and merits further testing in the clinical setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5660. doi:1538-7445.AM2012-5660