Engineering CAR T Cells to Target the HIV Reservoir DOI Creative Commons
Wenli Mu, Mayra A. Carrillo, Scott G. Kitchen

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2020, Номер 10

Опубликована: Авг. 13, 2020

The HIV reservoir remains to be a difficult barrier overcome in order achieve therapeutic cure for HIV. Several strategies have been developed purge the reservoir, including "kick and kill" approach, which is based on notion that reactivating latent will allow subsequent elimination by host anti-HIV immune cells. However, clinical trials testing certain classes of latency agents (LRAs) so far revealed minimal impact reducing viral reservoir. A robust response reactivated expressing cells critical this strategy work. current focus enhance immunity through use chimeric antigen receptors (CARs). Currently, HIV-specific CARs are being applied peripheral T cells, NK stem boost recognition killing infected In review, we summarize developments engineering directed CAR-expressing facilitate elimination. We also LRAs "kick" how new generation combinations with specific CAR cell therapies could provide an optimal target clearance from body.

Язык: Английский

In vivo killing of primary HIV-infected cells by peripheral-injected early memory–enriched anti-HIV duoCAR T cells DOI Creative Commons
Kim Anthony-Gonda, Alex Ray, Hang Su

и другие.

JCI Insight, Год журнала: 2022, Номер 7(21)

Опубликована: Ноя. 7, 2022

HIV-specific chimeric antigen receptor–T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with (PWH) by eliminating reactivated HIV-infected cells derived from latently infected within the reservoir. Paramount translating such therapeutic successfully into clinic will require anti-HIV CAR localize lymphoid tissues body and eliminate as CD4+ monocytes/macrophages. Here we show that i.v. injected duoCAR cells, generated using a clinical-grade lentiviral vector, localized site of active spleen humanized mice eliminated PBMCs. CyTOF analysis preinfusion revealed an early memory phenotype composed predominantly CCR7+ stem cell–like/central (TSCM/TCM) expression some effector-like molecules. In addition, effectively sense kill Furthermore, demonstrate efficient genetic modification PWH on suppressive ART subsequently autologous PBMCs superinfected HIV. These studies support safety efficacy therapy our presently open phase I/IIa clinical trial (NCT04648046).

Язык: Английский

Процитировано

29
Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques DOI Creative Commons
Helen L. Wu, Kathleen Busman‐Sahay, Whitney C. Weber

и другие.

Immunity, Год журнала: 2023, Номер 56(7), С. 1649 - 1663.e5

Опубликована: Май 25, 2023

Язык: Английский

Процитировано

19
The initial interplay between HIV and mucosal innate immunity DOI Creative Commons

Valeria Caputo,

Martina Libera,

Sofia Sisti

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Янв. 30, 2023

Human Immunodeficiency Virus (HIV) is still one of the major global health issues, and despite significant efforts that have been put into studying pathogenesis HIV infection, several aspects need to be clarified, including how innate immunity acts in different anatomical compartments. Given nature as a sexually transmitted disease, demands particular attention mucosal immune response. this scenario, we focused our on interplay between response: mucosae act physical barrier, whose integrity can compromised by virus-cell interaction induces In addition, explored role microbiota facilitating or preventing infection highlighted its changes could influence development opportunistic infections. Although recent progress, proper characterization response missing, further studies are needed understand they helpful for formulation an effective vaccine.

Язык: Английский

Процитировано

18
Robust expansion of HIV CAR T cells following antigen boosting in ART-suppressed nonhuman primates DOI Open Access
Blake J. Rust, Leslie S. Kean, Lucrezia Colonna

и другие.

Blood, Год журнала: 2020, Номер 136(15), С. 1722 - 1734

Опубликована: Июль 2, 2020

Язык: Английский

Процитировано

45
Engineering CAR T Cells to Target the HIV Reservoir DOI Creative Commons
Wenli Mu, Mayra A. Carrillo, Scott G. Kitchen

и другие.

Frontiers in Cellular and Infection Microbiology, Год журнала: 2020, Номер 10

Опубликована: Авг. 13, 2020

The HIV reservoir remains to be a difficult barrier overcome in order achieve therapeutic cure for HIV. Several strategies have been developed purge the reservoir, including "kick and kill" approach, which is based on notion that reactivating latent will allow subsequent elimination by host anti-HIV immune cells. However, clinical trials testing certain classes of latency agents (LRAs) so far revealed minimal impact reducing viral reservoir. A robust response reactivated expressing cells critical this strategy work. current focus enhance immunity through use chimeric antigen receptors (CARs). Currently, HIV-specific CARs are being applied peripheral T cells, NK stem boost recognition killing infected In review, we summarize developments engineering directed CAR-expressing facilitate elimination. We also LRAs "kick" how new generation combinations with specific CAR cell therapies could provide an optimal target clearance from body.

Язык: Английский

Процитировано

41