Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells
| Autor: | Nithianandan Selliah, Richard P. Junghans, Gautam K. Sahu, Kaori Sango, Qiangzhong Ma, Gail Skowron |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Cytotoxicity
Immunologic CD3 Complex Recombinant Fusion Proteins T-Lymphocytes medicine.medical_treatment Cytotoxicity Human immunodeficiency virus (HIV) CD4–CD28–CD3ζ HIV Infections Biology medicine.disease_cause Article Cell Line 03 medical and health sciences 0302 clinical medicine CD28 Antigens Virology medicine Humans Secretion Chimeric antigen receptor Latency (engineering) Designer T cells 030304 developmental biology 0303 health sciences Effector env Gene Products Human Immunodeficiency Virus HIV virus diseases Reactivation of latent HIV Immunotherapy 3. Good health Receptors Antigen Cell culture 030220 oncology & carcinogenesis CD4 Antigens Immunology HIV-1 Gene-modified T cells |
| Zdroj: | Virology. (1-2):268-275 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2013.08.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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