Abstract B021: Canine CAR T-cells therapy for mammary carcinoma in dogs

Abstract

Abstract In women, ductal carcinoma in situ (DCIS) is an often-diagnosed breast disease that is widely considered to be a nonobligate precursor of invasive carcinoma. TNBC is the most aggressive and lethal form of breast cancer and predominantly occurs in women at high genetic risk including those with mutated BRCA1 genes. We provide for the first time an immunocompetent animal model for triple-negative DCIS (TN-DCIS) that will facilitate molecular analysis of preinvasive TNBC and will provide an invaluable resource for identifying and selecting targets for TNBC vaccine immunoprevention or immunotherapeutic intervention. Unlike most studied rodent models, dogs develop TN-DCIS spontaneously without genetic or chemical manipulation. We have shown that canine DCIS resembles human DCIS with shared histopathologic and molecular features and with similar imaging and behavioral characteristics. Dogs are much more outbred than laboratory rodents, yet certain breeds are at increased risk for developing mammary tumors. Indeed, we have found that 50% of randomly screened asymptomatic hound dogs have premalignant mammary lesions and that mammary TN-DCIS often progresses to invasive carcinoma within one year. Given the many common features of canine breast cancer and the high homology between the canine and human genome, the dog model offers an outstanding opportunity for exploiting TNBC immunoprevention and immunotherapeutic strategies. Moreover, the prevalence and rapid progression of canine TN-DCIS provides a much more rapid and cost-effective alternative to human trials for evaluation of the clinical effectiveness of cancer vaccine strategies. One immunotherapeutic strategy we are testing using our canine TN-DCIS model is chimeric antigen receptor (CAR) T-cells. CAR T-cells have shown promise in treating many malignancies, but in solid tumors have been hindered by many limitations. To overcome these limitations, we designed genetically engineered universal canine CAR T-cells that must be activated and targeted by a small-molecule adaptor before it can kill cancer cells. Our results showed that universal CAR T cells are functional and killed canine mammary tumor cell lines in vitro. Citation Format: Xavier E. Ramos-Cardona, Sulma I. Mohammed, Yong Gu Lee, Phillip Low. Canine CAR T-cells therapy for mammary carcinoma in dogs [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B021.