Effect of Chidamide Combined With CAT-T or TCR-T Cell Therapy on HIV-1 Latent Reservoir
Study Details
Study Description
Brief Summary
To study the safety and effectiveness of the combination of Chidamide with Chimeric Antigen Receptor(CAR)-T or T cell receptor(TCR)-T cell therapy on HIV patients based on cART.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Despite the advent of combined antiretroviral therapy (cART), the persistence of viral reservoirs remains a major barrier to cure human immunodeficiency virus type 1 (HIV-1) infection. Recently, the shock and kill strategy, by which such reservoirs are eradicated following reactivation of latent HIV-1 by latency-reversing agents (LRAs), has been extensively practiced. It is important to reestablish virus-specific and reliable immune surveillance to eradicate the reactivated virus-harboring cells. Some studies have shown that Chidamide can highly activate the HIV reservoirs. The VC-CAR-T cells effectively induced the cytolysis of LRA-reactivated HIV-1-infected CD4 T lymphocytes isolated from infected individuals receiving suppressive cART. Our previous study demonstrated that the special features of genetically engineered CAR-T cells make them a particularly suitable candidate for therapeutic application in efforts to reach a functional HIV cure. The purpose of this study is to evaluate the safety and efficacy of Chidamide together with Chimeric Antigen Receptor(CAR)-T or T cell receptor(TCR)-T cell therapy based on cART in HIV-infected adults whose plasma HIV has been successfully suppressed after cART.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chidamide combined with CAR-T or TCR-T cell therapy Receiving chidamide combined with CAR-T or TCR-T cell therapy based on based on cART after attaining plasma HIV suppression (plasma HIV RNA <50 cp/ ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART without active HCV or HBV infection or opportunistic infections. |
Biological: Chidamide with CAR-T or TCR-T cell therapy
HIV-1 specific therapy
|
| No Intervention: without intervention Not receiving chidamide combined with CAR-T or TCR-T cell therapy but continuing cART after attaining plasma HIV suppression (plasma HIV RNA <50 cp/ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART, without active HCV or HBV infection or opportunistic infections. |
Outcome Measures
Primary Outcome Measures
- Incidence of treatment-associated adverse events [6 Months]
To observe the adverse events of intervention n HIV-infected patients during the study.
Secondary Outcome Measures
- HIV reservoir [6 Months]
To assay the HIV loads in the peripheral blood Mono-nuclear cells and plasma
Other Outcome Measures
- HIV-specific immunity [6 Months]
The number of HIV-specific CD4,CD8,VC-CAR-T and TCR-T cells after receiving the therapy.
Eligibility Criteria
Criteria
Inclusion Criteria:
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HIV infection confirmed
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Receiving cART more than 12 months.
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HIV viral-load < 50 copies/ml and CD4 cell count more than 350 cells/ul.
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Without serious liver , heart, liver and kidney diseases.
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The subjects know about the study and volunteer to attend the research and sign the informed consent.
Exclusion Criteria:
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With active HBV or HCV infection, or serious opportunistic infections.
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With serious chronic disease such like diabetes, the mental illness,et al
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History of suffering from pancreatitis during cART .
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Pregnant or breast-fed.
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With poor adherence.
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Unable to complete follow up.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Guangzhou 8th People's Hospital | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Guangzhou 8th People's Hospital
- Sun Yat-sen University
Investigators
- Principal Investigator: Weiping Cai, Bachelor, Guangzhou 8th People's Hospital China, Guangdong
Study Documents (Full-Text)
None provided.More Information
Publications
- Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014 Jan;257(1):107-26. doi: 10.1111/imr.12131. Review.
- Kobayashi Y, Gélinas C, Dougherty JP. Histone deacetylase inhibitors containing a benzamide functional group and a pyridyl cap are preferentially effective human immunodeficiency virus-1 latency-reversing agents in primary resting CD4+ T cells. J Gen Virol. 2017 Apr;98(4):799-809. doi: 10.1099/jgv.0.000716. Epub 2017 Apr 27.
- Kuai Q, Lu X, Qiao Z, Wang R, Wang Y, Ye S, He M, Wang Y, Zhang T, Wu H, Ren S, Yu Q. Histone deacetylase inhibitor chidamide promotes reactivation of latent human immunodeficiency virus by introducing histone acetylation. J Med Virol. 2018 Sep;90(9):1478-1485. doi: 10.1002/jmv.25207. Epub 2018 May 25.
- Liu C, Ma X, Liu B, Chen C, Zhang H. HIV-1 functional cure: will the dream come true? BMC Med. 2015 Nov 20;13:284. doi: 10.1186/s12916-015-0517-y. Review.
- Yang W, Sun Z, Hua C, Wang Q, Xu W, Deng Q, Pan Y, Lu L, Jiang S. Chidamide, a histone deacetylase inhibitor-based anticancer drug, effectively reactivates latent HIV-1 provirus. Microbes Infect. 2018 Oct - Nov;20(9-10):626-634. doi: 10.1016/j.micinf.2017.10.003. Epub 2017 Nov 8.
- 20171126V1