Preclinical Development of Therapeutics in Murine Models of Lung Cancer

Division Of Basic Sciences - Nci

Investigators

Abstract

CAPR developed novel PDX models for both non-small cell and small cell lung cancer in collaboration with investigators at the NIH Clinical Center. Nineteen PDX models representing unique osimertinib-resistant, epidermal growth factor receptor (EGFR)-driven lung tumors were evaluated for histopathology and sensitivity to drug combinations. In addition, the staff created PDXs from 20 patients with relapsed small cell lung cancer as part of a clinical trial exploring sensitivities to novel treatments. To characterize these novel models molecularly, CAPR scientists conducted high-throughput flow cytometry screening of SCLC tumor associated antigens using 5 clinically representative PDXs. As these PDXs were established and characterized from patients enrolled in NCI clinical trials, CAPR preclinical experts initiated the process of examine the efficacy, tumor immune infiltration, and abundance of response biomarkers in efficacy studies in which mice carrying newly established tumor models were subjected to to CAR-NKT, B7-H3 CAR T-cell treatments, as well as two potential novel targets that emerged from this RFA aim 1 for clinical translation. These lung cancer model types represent valuable resources toward finding novel therapies for recalcitrant lung cancer.