期刊
MOLECULAR THERAPY-ONCOLYTICS
卷 8, 期 -, 页码 14-26出版社
CELL PRESS
DOI: 10.1016/j.omto.2017.12.001
关键词
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资金
- Investors in Tocagen Inc.
- ABC2 Foundation (Washington, DC)
- National Brain Tumor Society (Watertown, MA)
- American Brain Tumor Association (Chicago, IL)
- Musella Foundation (Hewlett, NY)
- Voices against Brain Cancer (New York, NY)
- National University
Treatment of tumors with Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, followed by 5-fluorocytosine (5-FC) kills tumors by local production of 5-fluorouracil (5-FU). In brain tumor models, this treatment induces systemic anti-tumor immune responses and long-term immunemediated survival. Phase 1 Toca 511 and Toca FC (extendedrelease 5-FC) clinical trials in patients with recurrent high-grade glioma show durable complete responses and promising survival data compared to historic controls. The work described herein served to expand on our earlier findings in two models of metastatic colorectal carcinoma (mCRC). Intravenous (i.v.) delivery of Toca 511 resulted in substantial tumor-selective uptake of vector into metastatic lesions. Subsequent treatment with 5-FC resulted in tumor shrinkage, improved survival, and immune memory against future rechallenge with the same CT26 CRC cell line. Similar results were seen in a brain metastasis model of mCRC. Of note, 5-FC treatment resulted in a significant decrease in myeloid-derived suppressor cells (MDSCs) in mCRC tumors in both the liver and brain. These results support the development of Toca 511 and Toca FC as a novel immunotherapeutic approach for patients with mCRC. A phase 1 study of i.v. Toca 511 and Toca FC in solid tumors, including mCRC, is currently underway (NCT02576665).
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