Unknown

Dataset Information

0

A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces Immune Memory in Metastatic Colorectal Cancer Models.


ABSTRACT: 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 immune-mediated survival. Phase 1 Toca 511 and Toca FC (extended-release 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).

SUBMITTER: Yagiz K 

PROVIDER: S-EPMC5751967 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces Immune Memory in Metastatic Colorectal Cancer Models.

Yagiz Kader K   Rodriguez-Aguirre Maria E ME   Lopez Espinoza Fernando F   Montellano Tiffany T TT   Mendoza Daniel D   Mitchell Leah A LA   Ibanez Carlos E CE   Kasahara Noriyuki N   Gruber Harry E HE   Jolly Douglas J DJ   Robbins Joan M JM  

Molecular therapy oncolytics 20171205


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 immune-mediated survival. Phase 1 Toca 511 and Toca FC (extended-release 5-FC) clinical trials in patients with recurrent high-grade glioma show durable complete responses and promising survival data compar  ...[more]

Similar Datasets

| S-EPMC4761857 | biostudies-literature
| 2200169 | ecrin-mdr-crc
2015-11-01 | GSE72955 | GEO
2015-11-01 | E-GEOD-72955 | biostudies-arrayexpress
| S-EPMC6422008 | biostudies-literature
| S-EPMC7197216 | biostudies-literature
| S-EPMC2788826 | biostudies-literature
| S-EPMC6481342 | biostudies-literature
| S-EPMC5363416 | biostudies-literature
| S-EPMC4326030 | biostudies-literature