Dataset Information

T Cell Therapy Targeted on HLA-A02 Restricted HIV Antigen Epitopes: An Open Label Cellular Therapy Trial Using CD8+ T Cell.

ABSTRACT: Objective: To test the safety and efficacy of a T cell therapy de novo targeting HLA-A02 restricted HIV antigen epitopes. Design: This was a prospective open label clinical trial, which enrolled 28 HIV+ participants and 24 of them finished the trial. The study was publicly registered at Chinese Clinical Trial Registry, www.chictr.org.cn(ChiCTR-ICR-15005775). Method: Autologous peripheral blood mononuclear cells were co-cultured with HLA-A02 restricted HIV antigen epitopes peptides to produce cell product for this therapy. The trial was divided into five time-points with the same interval period for infusion of the cell products or monitoring parameters. Symptoms, vital signs, and blood samples were collected to analyze the safety and efficacy of this therapy. Results: Two cases of adverse effects happened during this trial in test group, which recovered without medical intervention. There was no severe adverse effect that occurred. Both symptoms and laboratory tests have no statistical significant difference between test and control group. Flowcytometry analysis showed the expression of the PD-1 and CD95 molecule on the cell surface were downregulated post-treatment in the test group. Conclusions: This autologous HIV-antigen specific effector CD8+ T cellular therapy was safe. It might have an impact on immune suppression that can provide useful reference to future cell therapy trials.

SUBMITTER: Liu S

PROVIDER: S-EPMC6435000 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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T Cell Therapy Targeted on HLA-A02 Restricted HIV Antigen Epitopes: An Open Label Cellular Therapy Trial Using CD8+ T Cell.

Liu Sai S Sun Jianping J Li Zhen Z Qin Ling L Liu Guihai G Li Kang K Wu Hao H Dong Tao T Zhang Yonghong Y

Frontiers in immunology 20190318

Objective: To test the safety and efficacy of a T cell therapy de novo targeting HLA-A02 restricted HIV antigen epitopes. Design: This was a prospective open label clinical trial, which enrolled 28 HIV+ participants and 24 of them finished the trial. The study was publicly registered at Chinese Clinical Trial Registry, www.chictr.org.cn(ChiCTR-ICR-15005775). Method: Autologous peripheral blood mononuclear cells were co-cultured with HLA-A02 restricted HIV antigen epit ...[more]

PMID: 30941124

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Project description:BACKGROUND: All four dengue virus (DV) serotypes (D1V, D2V, D3V and D4V) can cause a series of disorders, ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). Previous studies have revealed that DV serotype-specific CD8(+) T cells are involved in controlling DV infection. Serotype cross-reactive CD8(+) T-cells may contribute to the immunopathogenesis of DHF/DSS. The aim of the study was to identify HLA-A*0201-binding peptides from four DV serotypes. We then examined their immunogenicity in vivo and cross-reactivity within heterologous peptides. METHODS: D1V-derived candidate CD8(+) T-cell epitopes were synthesized and evaluated for their affinity to the HLA-A*0201 molecule. Variant peptides representing heterologous D2V, D3V, D4V serotypes were synthesized. The immunogenicity of the high-affinity peptides were evaluated in HLA-A*0201 transgenic mice. RESULTS: Of the seven D1V-derived candidate epitopes [D1V-NS4a(56-64)(MLLALIAVL), D1V-C(46-54)(LVMAFMAFL), D1V-NS4b(562-570)(LLATSIFKL), D1V-NS2a(169-177)(AMVLSIVSL), D1V-NS4a(140-148)(GLLFMILTV), D1V-NS2a(144-152)(QLWAALLSL) and D1V-NS4b(183-191)(LLMRTTWAL)], three peptides [D1V-NS4a(140-148), D1V-NS2a(144-152) and D1V-NS4b(183-191)] had a high affinity for HLA-A*0201 molecules. Moreover, their variant peptides for D2V, D3V and D4V [D2V-NS4a(140-148)(AILTVVAAT), D3V-NS4a(140-148)(GILTLAAIV), D4V-NS4a(140-148)(TILTIIGLI), D2V-NS2a(144-152)(QLAVTIMAI), D3V-NS2a(144-152)(QLWTALVSL), D4V-NS2a(143-151)(QVGTLALSL), D2V-NS4b(182-190)(LMMRTTWAL), D3V-NS4b(182-190) (LLMRTSWAL) and D4V-NS4b(179-187)(LLMRTTWAF)] also had a high affinity for HLA-A*0201 molecules. Furthermore, CD8+ T cells directed to these twelve peptides were induced in HLA-A*0201 transgenic mice following immunization with these peptides. Additionally, cross-reactivity within four peptides (D1V-NS4b(183-191), D2V-NS4b(182-190), D3V-NS4b(182-190) and D4V-NS4b(179-187)) was observed. CONCLUSIONS: Two novel serotype-specific HLA-A*0201-restricted CD8(+) T-cell epitopes (NS4a(140-148) and NS2a(144-152)) and one cross-reactive HLA-A*0201-restricted CD8(+) T-cell epitopes which is similar to a previously identified epitope were identified in D1V-D4V. Combining prediction algorithms and HLA transgenic mice is an effective strategy to identify HLA-restricted epitopes. Serotype-specific epitopes would be used to determine the protective role of serotype-specific CD8(+) T cells, while cross-reactive epitopes may provide assistance in exploring the role of serotype cross-reactive CD8(+) T cells in the immunopathogenesis of DHF/DSS.

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Dataset Information

T Cell Therapy Targeted on HLA-A02 Restricted HIV Antigen Epitopes: An Open Label Cellular Therapy Trial Using CD8+ T Cell.

Publications

T Cell Therapy Targeted on HLA-A02 Restricted HIV Antigen Epitopes: An Open Label Cellular Therapy Trial Using CD8+ T Cell.

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