Project 3 - Abstract Project 3 seeks to determine whether specific modifications to CD4 CAR T cells can enhance their ability to suppress HIV and reduce the latent HIV reservoir. These modifications include protecting CAR T cells from T cell exhaustion and infection, improving the frequency and tissue distribution of these cells, and ultimately exploring whether they can synergize with latency reversing agents (LRA) and CD19 B cell-specific CAR Ts to co-target HIV and B cell cancer. Specifically, we will leverage the expertise of Project 1 (prevent or reverse T cell exhaustion), Core B (preferred CAR integration sites), and Project 4 (CAR T manufacturing platform) to build upon our preliminary data demonstrating the ability of CD4 CAR T cells to suppress HIV in vivo. We will test these concepts in vivo utilizing a humanized mouse model that infuses T cells from well-controlled HIV-infected individuals to accomplish the following goals:
Aim 1 : Identify approaches to protect CD4 CAR T cells from dysfunction in vivo.
AIM 2 : Identify approaches to enhance the frequency and tissue distribution CD4 CAR T cells in vivo.
Aim 3 : Determine the in vivo efficacy of CAR T cells to co-target the HIV reservoir and CD19+ tumors. Therefore, utilizing a humanized mouse model of HIV infection, we hypothesize that enhanced CD4 CAR T cells will be capable of controlling HIV and targeting the HIV reservoir, providing insight into the mechanisms required to achieve a functional HIV cure

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI149680-01
Application #
9891737
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2020-05-15
Project End
2025-04-30
Budget Start
2019-12-01
Budget End
2020-11-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104