KSEF R&D Excellence: Lung Cancer Cell Lines as a Model for Tumor Mediated Evasion of Immunity

The current proposal will utilize tumor cell lines and clones derived from non small cell lung cancer (NSCLC) biopsies. Generation of TC lines in NSCLC is difficult. The PI has developed appropriate cell culture technique for TC generation which is successful roughly 18% of the time. The clones were generated from early passages. Both parental lines and clones will be used to study susceptibility of NSCLC to both immune effector mechanisms and the standard chemotherapeutic agent Cisplatin. The hypothesis stated is that single agent therapies do not provide long term cure. The PI suggests due to the heterogeneity of tumor cell populations, single agent therapies such as chemotherapy and immunotherapy may eliminate a % of the disease but cells exist which are either or both chemo resistant or immuno resistant. The clones that have been developed provide the heterogeneity which is necessary to study combination therapies in order to provide 100% kill of the tumor cell populations. The PI has developed cell lines from 7 NSCLC biopsies, 5-adenocarcinoma and 2-squamous cell carcinoma. The current study will evaluate one of each. The study will utilize standard cell culture, RT-PCR, cell surface phentotyping, and microcytotoxicity assays. The study is designed for a two year period of time. Results from the analysis will provide important information concerning the heterogeneity of tumor cell populations and susceptibility to therapeutic interventions. Pilot data obtained will be used to secure significant funding from the NIH for further studies designed to improve current therapeutic interventions in NSCLC. The PI believes the studies described will have direct impact on the citizens of the Commonwealth of Kentucky.