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- Title
Pancreatic cancer escape variants that evade immunogene therapy through loss of sensitivity to IFN?-induced apoptosis.
- Authors
Mazzolini, G; Narvaiza, I; Martinez-Cruz, L A; Arina, A; Barajas, M; Galofre, J C; Qian, C; Mato, J M; Prieto, J; Melero, I
- Abstract
Combined injections into experimental tumor nodules of adenovirus encoding IL-12 and certain chemokines are capable to induce immune-mediated complete regressions. In this study, we found that the combination of two adenoviruses, one encoding IL-12 and other MIP3α (Ad-CMVIL-12+AdCMVMIP3α) was very successful in treating CT-26-derived colon carcinomas. However, in experimental tumors generated from the pancreatic carcinoma cell line Panc02 such combined treatment induces 50% of macroscopic complete regressions, although local relapses within 1 week are almost constant. We derived cell lines from such relapsing tumors and found that experimental malignancies derived from their inoculum were not amenable to treatment in any case with AdCMVIL-12+AdCMVMIP-3α. Importantly, relapsing cell lines were insensitive to in vitro induction of apoptosis by IFNγ, in clear contrast with the original Panc02 cells. Comparative analyses by cDNA arrays of relapsing cell lines versus wild-type Panc02 were performed revealing an important number of genes (383) whose expression levels were modified more than two-fold. These changes grouped in certain gene ontology categories should harbor the mechanistic explanations of the acquired selective resistance to IFNγ.
- Subjects
CHEMOKINES; REGRESSION analysis; ADENOVIRUS diseases; CANCER; CELL lines
- Publication
Gene Therapy, 2003, Vol 10, Issue 13, p1067
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3301957