Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS

Zhen A, et al. (2017). PLOS Pathogens 13(12): e1006753

Speaker: Sen-Mao Tien (田森貿)                                     Time: 15:00~16:00, May 09, 2018

Commentator: Dr. Chih-Peng Chang (張志鵬 老師)     Place: Room 601

Abstract

        Acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection is one of the life-long chronic disease despite the success of combinational antiretroviral therapy (cART) in preventing disease progression and controlling HIV replication. The treatment of HIV infection by gene therapy has been a goal for decades. The chimeric antigen receptor (CAR) technology has created a new idea for treatment of HIV infection, but has only been applied in peripheral blood T-cells. Hematopoietic Stem/Progenitor Cells (HSPCs) can treat many infectious diseases and be capable of long-term engraftment. HSPCs-based CAR therapy has many advantages than T cell therapy. The authors used a protective CD4 chimeric antigen receptor (C46CD4CAR) to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV) infection in pigtail macaques. The in vitro results showed that C46CD4CAR cells are protected against HIV infection and respond functionally and specifically to HIV antigen in non-human primate (NHP) cells. In NHP animal model, the cART withdrawal resulted in lower viral rebound in CAR animals compared to control animals. Furthermore, the authors found that CAR-containing cells in NHP are capable of antigen-specific expansion and persistent almost two years after transplantation. They observed wide distribution of CAR-expressing cells that decreased SHIV RNA levels in gastrointestinal tract and lymphoid tissues. In summary from the in vitro and in vivo studies, the HSPC-based CAR therapy could generate long-term anti-HIV immunity in a preclinical NHP model.

References:

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