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A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
Published on: October 16, 2018
CAR-T cell Therapies for B-cell Lymphoid Malignancies: Identifying Targets Beyond CD19
Yenny M Vanegas1, Razan Mohty1, Martha E Gadd1
1Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA.
Abstract:
Chimeric antigen receptors (CARs) are synthetic engineered receptors with an antigen recognition domain derived from a high-specificity monoclonal antibody that can target surface molecules on tumor cells. T cells are genetically engineered to express CARs, thereby harnessing the antigen-recognition ability of antibodies and effector function of T cells. Target surface molecule selection is crucial for manufacturing CARs. Ideally, a target surface molecule should be restricted to tumor cells and minimally expressed or absent on normal tissues. Different CD19-targeted CAR-T cell therapies have been approved for the treatment of B-cell lymphoid malignancies that are refractory to other therapies, including indolent and aggressive B-cell non-Hodgkin lymphomas (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). Despite impressive results, many patients with aggressive and refractory B-cell malignancies do not respond to or relapse after CD19 CAR-T cell therapies. Thus, several additional strategies are currently being evaluated to overcome these limitations. This review discusses studies on other promising CAR-T cell targets, including CD20, CD22, BAFF-R, ROR1, CD70, BCR complex, kappa/lambda light chains, multitargeted CAR-T cells, and combinations of CAR-T cell therapy with different drugs.
Insights
Chimeric antigen receptor (CAR)-T cell therapy shows promise for B-cell malignancies. Researchers are exploring new targets beyond CD19 to improve treatment efficacy for patients who do not respond or relapse.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Chimeric antigen receptors (CARs) are engineered T cells that leverage antibody specificity to target tumor cells.
- Current CD19-targeted CAR-T cell therapies are approved for B-cell lymphoid malignancies but face challenges with non-responders and relapse.
- Identifying tumor-specific surface molecules is critical for effective CAR manufacturing.
Purpose of the Study:
- To review emerging CAR-T cell targets beyond CD19 for B-cell malignancies.
- To discuss strategies for overcoming limitations of current CAR-T cell therapies.
- To explore combinations of CAR-T cell therapy with other treatments.
Main Methods:
- Literature review of studies on novel CAR-T cell targets.
- Analysis of therapeutic strategies for refractory B-cell malignancies.
- Discussion of potential combination therapies.
Main Results:
- CD19 CAR-T cell therapy is effective for some B-cell malignancies but not all patients respond or remain in remission.
- Several alternative targets like CD20, CD22, BAFF-R, ROR1, CD70, BCR complex, and light chains are under investigation.
- Multitargeted CAR-T cells and combination therapies show potential to enhance efficacy.
Conclusions:
- New CAR-T cell targets and combinatorial approaches are essential to improve outcomes for patients with refractory B-cell malignancies.
- Further research is needed to optimize these novel strategies and broaden their clinical application.
- Advancing CAR-T cell therapy requires exploring diverse targets and treatment combinations.
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