The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity.

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2022-06-21

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Abstract

CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). However, even second- generation anti-CD30 CAR T-cells with CD28 (28z) costimulatory domains failed to achieve the desired rate of complete responses. In the present study, we developed second-generation (CD28z) and third-generation (CD28BBz) CAR T-cells targeting CD30 and investigated their efficacy in vitro and in vivo. Both of CD28z and CD28BBz anti-CD30 CAR T cells were similar regarding amplification, T cell subsets distribution, T cell activity, effector/memory and exhaustion. However, we found that the 28BBz anti-CD30 CAR T-cells persist long-term, specifically homing to the tumor and mediating powerful antitumor activity in tumor xenograft models. Subsequently, we also demonstrated that the third generation anti-CD30 CAR T-cells have miner side effects or potential risks of tumorigenesis. Thus, anti-CD30 CAR T-cells represent a safe and effective treatment for Hodgkin lymphoma.

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10.1038/s41598-022-14523-0

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Zhang, Shangkun, Chaojiang Gu, Lifang Huang, Han Wu, Jiangzhou Shi, Zijian Zhang, Yong Zhou, Jingjiao Zhou, et al. (2022). The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity. Scientific reports, 12(1). p. 10488. 10.1038/s41598-022-14523-0 Retrieved from https://hdl.handle.net/10161/25444.

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Young

Ken H Young

Professor of Pathology

I am a clinically-oriented diagnostic physician with clinical expertise in the pathologic diagnosis of hematologic cancers including tumors of the bone marrow, lymphoid tissue, spleen and pre-malignant hematologic conditions. Another area of interest is blood cancer classification with molecular and genetic profiling. In my research program, we focus on molecular mechanisms of tumor progression, cell-of-origin, biomarkers, and novel therapeutic strategies in lymphoma, myeloma and leukemia. In addition to patient care and translational research, medical education and scientific communication are also part of interest. I provide persistent support for the physician-scientist program and Blood Cancer Pathology program in the department and cancer center. Many residents, fellows, graduates and postdocs have worked and been trained in our program. We perform comprehensive clinical and research functions that include bone marrow, lymphoma pathology, clinical flow cytometry, cytogenetics, molecular diagnostics and outside services.

I am currently the director of hematopathology division that provides diagnostic consultation services and relevant specialized testing for patients with various types of acute and chronic leukemia, lymphoma and benign hematologic disorders. I am specialized in the diagnosis of hematological disorders, including acute and chronic leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, B and T-cell lymphomas, Hodgkin lymphoma, cutaneous and orbital lymphomas and benign bone marrow and lymph node disorders. 

Our group has been supported by various funding resources since 2006 and has published 318 original peer-reviewed articles and 56 review articles, many in high- impact journals (Nature Clin Onc Rev, JCO, JAMA, Lancet, Blood, JHO, Leukemia and Clinical Cancer Research). The contributions to the hematology field include the development of novel diagnostic algorithms, molecular and genetic biomarkers for classification of blood cancer, lymphoid neoplasms and lymphoid diseases.




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