The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity.
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.
Duke Scholars
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- T-Lymphocytes
- Lymphoma, Large-Cell, Anaplastic
- Ki-1 Antigen
- Immunotherapy, Adoptive
- Humans
- Hodgkin Disease
- Antibodies
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- T-Lymphocytes
- Lymphoma, Large-Cell, Anaplastic
- Ki-1 Antigen
- Immunotherapy, Adoptive
- Humans
- Hodgkin Disease
- Antibodies