Development and Characterization Of Cell Lines Derived From Hamster Breast Carcinomas As Model Of Oncolytic Virotherapy

Abstract

Two models of breast cancer to study oncolytic virotherapy were investigated in female Syrian golden hamsters. In contrast to most other species examined, the Syrian hamster is permissive for human Adenovirus replication. Single doses of 2 carcinogens to 2 different groups of animals were administered: 7,12‐dimethylbenz[a]anthracene (DMBA) or N‐methylnitrosourea (MNU). Body weights, palpations and PET imaging for tumors were recorded. Animals were necropsied and tissues were taken for primary culture, histology and H&E staining. After cell lines were established from primary tumors, karyotyping, infectivity, oncolytic activity, and growth rate were determined. Both lines contain 74 chromosomes where normal for hamster is 44. Histology determined the DMBA line was derived from a highly aggressive, poorly differentiated carcinoma. When injected into nude mice xenografts, the DMBA derived line grew rapidly, invaded into underlying muscle, and metastasized to lung and bone. The MNU line, clearly an adenocarcinoma, was syngeneicly transplanted into recipient hamsters with a take rate of <50%; those tumors were harvested, grown in primary culture, and transplanted again with a take rate of 100%. The MNU line shows promising results for use in oncolytic virotherapy while the DMBA might prove to be useful in testing for failed drugs. Funding: Feist‐Weiller Cancer Center and the LA Gene Therapy Consortium