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Challenges and Opportunities of Using Adoptive T-Cell Therapy as Part of an HIV Cure Strategy.

ABSTRACT: HIV-infected individuals successfully controlling viral replication via antiretroviral therapy often have a compromised HIV-specific T-cell immune response due to the lack of CD4 T-cell help, viral escape, T-cell exhaustion, and reduction in numbers due to the withdrawal of cognate antigen. A successful HIV cure strategy will likely involve a durable and potent police force that can effectively recognize and eliminate remaining virus that may emerge decades after an individual undergoes an HIV cure regimen. T cells are ideally suited to serve in this role, but given the state of the HIV-specific T-cell response, it is unclear how to best restore HIV-specific T-cell activity prior initiation of a HIV cure strategy. Here, we review several strategies of generating HIV-specific T cells ex vivo that are currently being tested in the clinic and discuss how infused T cells can be part of an HIV cure strategy.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC7883023 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Challenges and Opportunities of Using Adoptive T-Cell Therapy as Part of an HIV Cure Strategy.

Zhou Yuqi Y Maldini Colby R CR Jadlowsky Julie J Riley James L JL

The Journal of infectious diseases 20210201 12 Suppl 2

HIV-infected individuals successfully controlling viral replication via antiretroviral therapy often have a compromised HIV-specific T-cell immune response due to the lack of CD4 T-cell help, viral escape, T-cell exhaustion, and reduction in numbers due to the withdrawal of cognate antigen. A successful HIV cure strategy will likely involve a durable and potent police force that can effectively recognize and eliminate remaining virus that may emerge decades after an individual undergoes an HIV c ...[more]

PMID: 33586770

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Project description:Rejection of solid organ transplant and graft versus host disease (GvHD) continue to be challenging in post transplantation management. The introduction of calcineurin inhibitors dramatically improved recipients' short-term prognosis. However, long-term clinical outlook remains poor, moreover, the lifelong dependency on these toxic drugs leads to chronic deterioration of graft function, in particular the renal function, infections and de-novo malignancies. These observations led investigators to identify alternative therapeutic options to promote long-term graft survival, which could be used concomitantly, but preferably, replace pharmacologic immunosuppression as standard of care. Adoptive T cell (ATC) therapy has evolved as one of the most promising approaches in regenerative medicine in the recent years. A range of cell types with disparate immunoregulatory and regenerative properties are actively being investigated as potential therapeutic agents for specific transplant rejection, autoimmunity or injury-related indications. A significant body of data from preclinical models pointed to efficacy of cellular therapies. Significantly, early clinical trial observations have confirmed safety and tolerability, and yielded promising data in support of efficacy of the cellular therapeutics. The first class of these therapeutic agents commonly referred to as advanced therapy medicinal products have been approved and are now available for clinical use. Specifically, clinical trials have supported the utility of CD4+CD25+FOXP3+ regulatory T cells (Tregs) to minimize unwanted or overshooting immune responses and reduce the level of pharmacological immunosuppression in transplant recipients. Tregs are recognized as the principal orchestrators of maintaining peripheral tolerance, thereby blocking excessive immune responses and prevent autoimmunity. Here, we summarize rationale for the adoptive Treg therapy, challenges in manufacturing and clinical experiences with this novel living drug and outline future perspectives of its use in transplantation.

Dataset Information

Challenges and Opportunities of Using Adoptive T-Cell Therapy as Part of an HIV Cure Strategy.

Publications

Challenges and Opportunities of Using Adoptive T-Cell Therapy as Part of an HIV Cure Strategy.

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