HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study
Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting t...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2364744 |
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| author | Tao Yang Zhiman Xie Zhe Xu Bo Tu Huan Lu Huihuang Huang Lei Huang Chao Zhang Liying Gao Lei Jin Ping Ma Jun Zou Limin Liu Cheng Zhen Chunbao Zhou Sirun Meng Yuan-Yuan Li Jin-Wen Song Shixiong Yang Hui-Sheng Ai Yanmei Jiao Ming Shi Ruonan Xu Fu-Sheng Wang |
| author_facet | Tao Yang Zhiman Xie Zhe Xu Bo Tu Huan Lu Huihuang Huang Lei Huang Chao Zhang Liying Gao Lei Jin Ping Ma Jun Zou Limin Liu Cheng Zhen Chunbao Zhou Sirun Meng Yuan-Yuan Li Jin-Wen Song Shixiong Yang Hui-Sheng Ai Yanmei Jiao Ming Shi Ruonan Xu Fu-Sheng Wang |
| author_sort | Tao Yang |
| collection | DOAJ |
| description | Recurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010–37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376. |
| format | Article |
| id | doaj-art-437226862c2d4cd3907b829d2e65b8c6 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-437226862c2d4cd3907b829d2e65b8c62025-08-20T02:37:32ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2364744HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a studyTao Yang0Zhiman Xie1Zhe Xu2Bo Tu3Huan Lu4Huihuang Huang5Lei Huang6Chao Zhang7Liying Gao8Lei Jin9Ping Ma10Jun Zou11Limin Liu12Cheng Zhen13Chunbao Zhou14Sirun Meng15Yuan-Yuan Li16Jin-Wen Song17Shixiong Yang18Hui-Sheng Ai19Yanmei Jiao20Ming Shi21Ruonan Xu22Fu-Sheng Wang23Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaInfectious Diseases Department, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaInfectious Diseases Department, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaDepartment of Infectious Diseases, Tianjin Second People’s Hospital, Tianjin, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaDepartment of Infectious Diseases, Tianjin Second People’s Hospital, Tianjin, People’s Republic of ChinaInfectious Diseases Department, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaInfectious Diseases Department, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaInfectious Diseases Department, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of ChinaSenior Department of Hematology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaRecurrent opportunistic infections (OIs) in patients with severely immunosuppressed AIDS remain an unresolved medical challenge despite advancements in antiretroviral therapy (ART). To address this gap, we developed an HLA-mismatched allogeneic adoptive immune therapy (AAIT) specifically targeting this patient population. The safety and efficacy of this novel therapeutic approach were preliminarily confirmed in our phase 1 trial. Subsequently, a multicenter, open-label, controlled, phase 2a trial was conducted to evaluate the efficacy of AAIT in combination with ART compared with the conventional ART-only regimen. No difference in the incidence of adverse events (AEs) was observed between the two groups at the 96-week follow-up. AAIT treatment improved CD4+ T cell recovery at weeks 72 (P = 0.048) and 96 (P = 0.024) compared to the Control Group. Additionally, stratified analysis of patients in the AAIT Group showed that donor/recipient sex mismatch was significantly associated with the likelihood of patients achieving an immunological response (OR = 8.667; 95% CI, 2.010–37.377; P = 0.004). These findings suggest that AAIT serves as a promising adjunct therapy for improving the outcomes of patients with severely immunosuppressed AIDS. Further studies are needed to elucidate the immunological mechanisms underlying AAIT and identify the subpopulations that respond optimally to this therapeutic approach. This trial is registered at www.clinicaltrials.gov (NCT04098770).Trial registration: ClinicalTrials.gov identifier: NCT04098770.Trial registration: ClinicalTrials.gov identifier: NCT02651376.https://www.tandfonline.com/doi/10.1080/22221751.2024.2364744AIDSallogeneiccell therapyclinical trailimmune restoration |
| spellingShingle | Tao Yang Zhiman Xie Zhe Xu Bo Tu Huan Lu Huihuang Huang Lei Huang Chao Zhang Liying Gao Lei Jin Ping Ma Jun Zou Limin Liu Cheng Zhen Chunbao Zhou Sirun Meng Yuan-Yuan Li Jin-Wen Song Shixiong Yang Hui-Sheng Ai Yanmei Jiao Ming Shi Ruonan Xu Fu-Sheng Wang HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study Emerging Microbes and Infections AIDS allogeneic cell therapy clinical trail immune restoration |
| title | HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study |
| title_full | HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study |
| title_fullStr | HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study |
| title_full_unstemmed | HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study |
| title_short | HLA-mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed AIDS: a multicenter, open-label, controlled, phase 2a study |
| title_sort | hla mismatched allogeneic adoptive immune therapy in patients with severely immunosuppressed aids a multicenter open label controlled phase 2a study |
| topic | AIDS allogeneic cell therapy clinical trail immune restoration |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2364744 |
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