Adoptive Cell Therapy Against Triple-Negative Breast Cancer Using a Novel tMUC1 Antibody-Derived CAR
Abstract
In the previous two reports, Tasks 1, 2, and 3 (Aim 1) were completed. Most of Takes 4, 5, 6, and 7 (Aim2a, 2b, 2c) were accomplished. Tasks 8, 9, 10 (Aim3) were initiated. In brief, post approval for IACUC and IRB protocols, we completed the development of the 2nd and 3rd generation human CAR constructs, confirmed the sequences, generated the CAR T cells, and successfully completed cytolysis assays against TNBC cell lines in an antigen-specific manner without any toxic effects to normal epithelial cells. We initiated the in vivo experiments outlined in specific aim 2. Most of the data is now published. We completed the efficacy study of human CAR T+anti-PD1blocking antibody treatment in the NSG mouse model of human TNBC. We successfully generated the murine CAR t cells and conducted in vitro functional assays using murine breast cancer cell lines. We started the efficacy evaluation of murine CAR t cells in an immune competent spontaneous PyVMT tumor model in vivo. In this cycle, we report theprogress made in Tasks 6 through 10. We complete the efficacy study of mouse CAR t cells in immune competenthuman MUC1.Tg mice. No significance is observed from mouse CAR t cell treatment, which we believe is largely due to CAR t cell penetration into tumor in this aggressive orthotopic model. We achieve a significant reduction for tumor growth and progression as well as overall mouse survival in mouse CAR t cell group in spontaneous PyVMT tumor model, which lasts over 5 months. We receive five breast cancer patient PDX samples and complete their MUC1expression profile. We establish the human tumor explant model with 2 PDX samples.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1156602
Entities
People
- Pinku Mukherjee
Organizations
- University of North Carolina at Charlotte