Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells.
The current antiretroviral therapy (ART) can effectively reduce plasma HIV loads to undetectable levels, but cannot eliminate latently infected resting memory CD4 T cells that persist for the lifetime of infected patients. Therefore, designing new therapeutic approaches to eliminate these latently infected cells or the cells that produce HIV upon reactivation from latency is a priority in the ART era in order to progress to a cure of HIV. Here, we show that "designer" T cells expressing chimeric antigen receptor (CAR), CD4-CD28-CD3ζ, can target and kill HIV Env-expressing cells. Further, they secrete effector cytokines upon contact with HIV Env+ target cells that can reactivate latent HIV in a cell line model, thereby exposing those cells to recognition and killing by anti-HIV CAR+ T cells. Taken to the limit, this process could form the basis for an eventual functional or sterilizing cure for HIV in patients.
HIV Biology and Persistence Laboratory, Roger Williams Medical Center, Providence, RI, USA; Division of Infectious Diseases, Roger Williams Medical Center, Providence, RI, USA. Electronic address: gsahu@rwmc.org.
Gautam K
GK
Sahu
Kaori
K
Sango
Nithianandan
N
Selliah
Qiangzhong
Q
Ma
Gail
G
Skowron
Richard P
RP
Junghans
D018106:CD28 Antigens / Q000096:biosynthesis* / Q000235:genetics; D017252:CD3 Complex / Q000096:biosynthesis* / Q000235:genetics; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000628:therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D011946:Receptors, Antigen / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000276:immunology*
D018106:CD28 Antigens; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D015704:CD4 Antigens; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins; D054299:env Gene Products, Human Immunodeficiency Virus
CD4–CD28–CD3ζ; Chimeric antigen receptor; Cytotoxicity; Designer T cells; Gene-modified T cells; HIV-1; Reactivation of latent HIV