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Chimeric antigen receptor T-cell therapies for multiple myeloma
| Content Provider | Scilit |
|---|---|
| Author | Mikkilineni, Lekha Kochenderfer, James N. |
| Copyright Year | 2017 |
| Description | Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR-T cells (CAR-Ts) against leukemia and lymphoma has encouraged development of CAR-T therapies for MM. Target antigens for CARs must be expressed on malignant cells, but expression on normal cells must be absent or limited. B-cell maturation antigen is expressed by normal and malignant plasma cells. CAR-Ts targeting B-cell maturation antigen have demonstrated significant antimyeloma activity in early clinical trials. Toxicities in these trials, including cytokine release syndrome, have been similar to toxicities observed in CAR-T trials for leukemia. Targeting postulated CD19+ myeloma stem cells with anti-CD19 CAR-Ts is a novel approach to MM therapy. MM antigens including CD138, CD38, signaling lymphocyte–activating molecule 7, and κ light chain are under investigation as CAR targets. MM is genetically and phenotypically heterogeneous, so targeting of >1 antigen might often be required for effective treatment of MM with CAR-Ts. Integration of CAR-Ts with other myeloma therapies is an important area of future research. CAR-T therapies for MM are at an early stage of development but have great promise to improve MM treatment. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731088/pdf |
| Ending Page | 2602 |
| Page Count | 9 |
| Starting Page | 2594 |
| DOI | 10.1182/blood-2017-06-793869 |
| Journal | Blood |
| Issue Number | 24 |
| Volume Number | 130 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2017-12-14 |
| Access Restriction | Open |
| Subject Keyword | Hematology Multiple Myeloma Treatment Leukemia Plasma Cells Antigen Promise Car Ts Car T Therapies Malignancy of Plasma Journal: Blood (Vol- 2005, Issue- 24) |
| Content Type | Text |
| Resource Type | Article |
