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Targeting TAG-72 in cutaneous T cell lymphoma
Vera J Evtimov1,2, Maree V Hammett1,2, Aleta Pupovac1,2
1Cartherics Pty Ltd, Notting Hill, Australia.
Heliyon
|September 12, 2024
Summary
Tumor associated glycoprotein-72 (TAG-72) is expressed on cutaneous T cell lymphoma (CTCL) cells, making it a potential target for CAR-T cell therapy. This study demonstrates TAG-72 CAR-T cells effectively target and eliminate CTCL cells both in vitro and in vivo.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Cutaneous T cell lymphoma (CTCL) treatments often require specific tumor targets absent on healthy cells.
- Tumor associated glycoprotein-72 (TAG-72), a target in solid tumors, has not been explored for hematological malignancies.
Purpose of the Study:
- To investigate TAG-72 as a potential therapeutic target for CTCL.
- To evaluate the efficacy of TAG-72-targeted chimeric antigen receptor (CAR)-T cells against CTCL.
Main Methods:
- Flow cytometry and immunohistochemistry assessed TAG-72 expression on CTCL cells and tissues.
- ELISA measured soluble TAG-72 (CA 72-4) in patient plasma.
- TAG-72 CAR-T cells were generated from healthy donors and CTCL patients for in vitro and in vivo functional assays.
Main Results:
- TAG-72 expression was significantly higher on CTCL T cells (CD3+, CD4+) compared to healthy donors.
- TAG-72 CAR-T cells specifically eradicated TAG-72+ CTCL cells in vitro.
- CAR-T cells derived from CTCL patients demonstrated in vivo efficacy in a xenograft model.
Conclusions:
- This study provides the first evidence of TAG-72 as a viable therapeutic target for CTCL.
- TAG-72 CAR-T cell therapy holds promise for treating CTCL.
