Adoptive Cell Therapy Against Triple-Negative Breast Cancer Using a Novel tMUC1 Antibody-Derived CAR
Abstract
In the previous three 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 started and partially finished. In brief, we successfully generated the 2nd generation CAR T cells, and completed cytolysis assays against TNBC cell lines in an antigen-specific manner. Part of the in vivo experiments outlined in specific aim 2 had been completed and is published. We completed the efficacy study of human CAR T+anti-PD1 blocking 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. The efficacy of murine CAR t cells in orthotopic implantation model were completed using MUC1.Tg mice and no significant tumor reduction was observed. We achieved a significant reduction for tumor growth and progression as well as overall mouse survival in mouse CAR t cell group in spontaneous MMT tumor model, which lasted over 5 months. We received five breast cancer patient PDX samples and complete their MUC1 expression profile. We established the human tumor explant model with 2 PDX samples. In this cycle, we report the progress we made to complete the project. We successfully made the 3rd generation CAR T cells, and completed cytolysis assays against TNBC cell lines. The rest portion of work in Task 4 and 5 are started. We completed the efficacy and toxicity evaluation of murine CAR t cells in spontaneous MMT tumor model in vivo, and its associated endpoint studies in Task 7. We completed in vivo passage of 2 TNBC PDX samples and made sufficient tissue stocks for Task 10. We made sufficient human CAR T cells for Task 10.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1190481
Entities
People
- Pinku Mukherjee
Organizations
- University of North Carolina at Charlotte