CAR T cells: Living HIV drugs

Abstract

Human immunodeficiency virus type 1 (HIV-1), the virus that causes AIDS (acquired immunodeficiency syndrome), is a major global public health issue. Although the advent of combined antiretroviral therapy (ART) has made significant progress in inhibiting HIV replication in patients, HIV-infected cells remain the principal cellular reservoir of HIV, this allows HIV to rebound immediately upon stopping ART, which is considered the major obstacle to curing HIV infection. Chimeric antigen receptor (CAR) cell therapy has provided new opportunities for HIV treatment. Engineering T cells or hematopoietic stem cells (HSCs) to generate CAR T cells is a rapidly growing approach to develop an efficient immune cell to fight HIV. Herein, we review preclinical and clinical data available for the development of CAR T cells. Further, the advantages and disadvantages of clinical application of anti-HIV CAR T cells will be discussed.

Developing CAR T and CAR NK cells for HIV-1 eradication

“…After attaching to the HIV envelope (env), CD4-CAR T cells demonstrated very strong cytolytic activity toward virally infected targets in vitro [7]. Although the infusion of CD4-CAR T cells into patients was safe and these T cells need time, the initial clinical studies did not achieve a sustained reduction of the HIV burden.…”

“…Although the infusion of CD4-CAR T cells into patients was safe and these T cells need time, the initial clinical studies did not achieve a sustained reduction of the HIV burden. The CAR design may adversely affect T cell function, and patients on ART are some of the potential contributing factors to the trial that failed to produce a continuous decline in viral load [7]. Additionally, the use of CD4 as the targeting motif has frequently been cited as the primary cause of failure in these clinical studies since it may have left the transduced CD8 + T cells [7].…”

“…The CAR design may adversely affect T cell function, and patients on ART are some of the potential contributing factors to the trial that failed to produce a continuous decline in viral load [7]. Additionally, the use of CD4 as the targeting motif has frequently been cited as the primary cause of failure in these clinical studies since it may have left the transduced CD8 + T cells [7]. The innovative CD4-CARs are created to co-express HIV-1 fusion inhibitors, block HIV-1 entry, and mediate viral RNA degradation, to avoid this circumstance [8].…”

Targeting the HIV reservoir: chimeric antigen receptor therapy for HIV cure

“…Immunotherapy has been extensively practiced to achieve HIV remission, [7] including chimeric antigen receptor (CAR) cell therapy. [8] The CAR is a synthetic modular protein aimed at redirecting immune cell reactivity toward a target of interest, [9] which consists of an extracellular antigen recognition domain and an intracellular signaling domain. The extracellular antigen recognition domain is a single-chain variable fragment (scFv) derived from a monoclonal antibody (mAb), which allows antigen recognition in a major histocompatibility complex (MHC)-unrestricted manner.…”

“…Immunotherapy has been extensively practiced to achieve HIV remission, [ 7 ] including chimeric antigen receptor (CAR) cell therapy. [ 8 ]…”