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Engineering TAG-72 and CD30 CAR-T Cells for T Cell Malignancies
Van To1,2, Vera J Evtimov1,2, Runzhe Shu1,2
1Cartherics Pty Ltd, Notting Hill, Victoria, Australia.
Background:
T cell malignancies represent a broad, highly heterogeneous subset of lymphomas with poor prognosis. Chimeric antigen receptor (CAR)-T cell therapy holds great promise in treating B cell lymphoma and multiple myeloma. However, understanding its efficacy in treating T cell lymphoma remains challenging, primarily due to the lack of tumor-specific targets and intra-tumor heterogeneity.
Methods:
In this proof-of-concept study, we developed and characterized three distinct CAR-T cells targeting tumor-associated glycoprotein 72 (TAG-72), C-C chemokine receptor type 4 (CCR4) and tumor necrosis factor receptor CD30 respectively and assessed their anti-tumor efficacy against T cell malignancies in vitro.
Results:
TAG-72 and CD30 CAR-T cells each demonstrated comparable expansion potential and eliminated tumor cells expressing their respective target antigens. Subsequently, we explored the advantages of targeting two antigens through the pooling of these CAR-T cells. In instances where target antigen expression was low (as determined by flow cytometry), dual targeting of TAG-72 and CD30 was able to elicit cytotoxic function.
Conclusion:
These findings define TAG-72 and CD30-targeting CAR-T cells as a promising strategy against T cell malignancies and highlight the potential of dual or combination CAR-T cell therapies for this aggressive disease.
