Related Experiment Video
Updated: Jul 30, 2025
08:46
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
53.4K
CD38 as a pan-hematologic target for chimeric antigen receptor T cells
Tina Glisovic-Aplenc1, Caroline Diorio1,2, John A Chukinas1
1Division of Oncology, Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, PA.
Blood Advances
|May 12, 2023
Summary
Chimeric antigen receptor (CAR) T-cell therapy targeting CD38 shows promise for treating multiple blood cancers. CART-38 effectively eliminated leukemia and myeloma in mice, offering a potential new treatment for diverse patients.
Area of Science:
- Immunotherapy
- Hematologic Malignancies
- Oncology
Background:
- Chemotherapy is often insufficient for curing hematologic malignancies, necessitating novel therapeutic strategies.
- Chimeric antigen receptor (CAR) T-cell therapy engineers T cells to target specific cancer antigens.
- CD38 is a validated target in multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL), and is overexpressed in acute myeloid leukemia (AML).
Purpose of the Study:
- To develop and evaluate human CD38-redirected T cells (CART-38) as a unified therapeutic approach for multiple CD38-expressing hematologic malignancies.
- To assess the efficacy and safety of CART-38 in preclinical models across the pediatric-to-adult age spectrum.
Main Methods:
- Development of human CART-38 cells targeting the CD38 antigen.
- In vitro assessment of CART-38 expansion and function on activated T cells.
- In vivo efficacy studies using xenograft mouse models with AML, T-ALL, and MM cell lines and primary samples.
- Evaluation of CART-38 effects on normal human hematopoiesis in a xenograft model.
Main Results:
- CD38 expression on activated T cells did not impede CART-38 expansion or in vitro function.
- CART-38 demonstrated efficacy in xenograft models, mediating rejection of AML, T-ALL, and MM, and prolonging survival.
- CART-38 treatment led to a reduction in hematopoietic progenitors in a normal hematopoiesis model, indicating a potential toxicity.
Conclusions:
- CART-38 represents a promising unified immunotherapy for CD38-expressing hematologic malignancies, including AML, T-ALL, and MM.
- The preclinical data support the potential of CART-38 to treat diverse patient populations across a wide age range.
- Careful monitoring for potential toxicities, such as effects on normal hematopoiesis, is warranted during clinical translation.
