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CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity.

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  • معلومة اضافية
    • المصدر:
      Publisher: Biomed Central Country of Publication: England NLM ID: 101468937 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8722 (Electronic) Linking ISSN: 17568722 NLM ISO Abbreviation: J Hematol Oncol Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: [London] : Biomed Central, 2008-
    • الموضوع:
      12E7 Antigen/*immunology ; Immunotherapy, Adoptive/*methods ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*therapy ; Receptors, Chimeric Antigen/*therapeutic use; 12E7 Antigen/antagonists & inhibitors ; Animals ; Blood Cells/drug effects ; Cell Line, Tumor ; Humans ; Immunotherapy, Adoptive/adverse effects ; Mice ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/immunology ; Receptors, Chimeric Antigen/immunology
    • نبذة مختصرة :
      CAR T cell therapy has shown dramatic clinical success in relapsed or refractory B-ALL and other hematological malignancies. However, the loss of specific antigens, cell fratricide, T cell aplasia, and normal T cell separation are challenges in treating T cell leukemia/lymphoma with CAR T therapy. CD99 is a promising antigen to target T-ALL and AML as it is strongly expressed on the majority of T-ALL and AML. Here, we isolated a low-affinity CD99 (12E7) antibody, which specifically recognizes leukemia cells over normal blood cells. Moreover, T cells transduced with an anti-CD99-specific CAR that contained the 12E7 scFv expanded with minor fratricide and without normal blood cells toxicity. We observed that our anti-CD99 CAR T cells showed robust cytotoxicity specifically against CD99+ T-ALL cell lines and primary tumor cells in vitro and significantly prolonged cell line-derived xenografts (CDXs) or patient-derived xenografts (PDXs) models survival in vivo. Together, our results demonstrate that anti-CD99 CAR T cells could specifically recognize and efficiently eliminate CD99+ leukemia cells.
      (© 2021. The Author(s).)
    • References:
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    • Contributed Indexing:
      Keywords: AML; Antitumor activity; CAR T; CD99; T-ALL
    • الرقم المعرف:
      0 (12E7 Antigen)
      0 (CD99 protein, human)
      0 (Receptors, Chimeric Antigen)
    • الموضوع:
      Date Created: 20211010 Date Completed: 20211122 Latest Revision: 20211122
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC8502293
    • الرقم المعرف:
      10.1186/s13045-021-01178-z
    • الرقم المعرف:
      34627328