Adoptive Cellular Therapy for Multiple Myeloma Using CAR- and TCR-Transgenic T Cells: Response and Resistance.
Franziska FüchslAngela M KrackhardtPublished in: Cells (2022)
Despite the substantial improvement of therapeutic approaches, multiple myeloma (MM) remains mostly incurable. However, immunotherapeutic and especially T cell-based approaches pioneered the therapeutic landscape for relapsed and refractory disease recently. Targeting B-cell maturation antigen (BCMA) on myeloma cells has been demonstrated to be highly effective not only by antibody-derived constructs but also by adoptive cellular therapies. Chimeric antigen receptor (CAR)-transgenic T cells lead to deep, albeit mostly not durable responses with manageable side-effects in intensively pretreated patients. The spectrum of adoptive T cell-transfer covers synthetic CARs with diverse specificities as well as currently less well-established T cell receptor (TCR)-based personalized strategies. In this review, we want to focus on treatment characteristics including efficacy and safety of CAR- and TCR-transgenic T cells in MM as well as the future potential these novel therapies may have. ACT with transgenic T cells has only entered clinical trials and various engineering strategies for optimization of T cell responses are necessary to overcome therapy resistance mechanisms. We want to outline the current success in engineering CAR- and TCR-T cells, but also discuss challenges including resistance mechanisms of MM for evading T cell therapy and point out possible novel strategies.
Keyphrases
- cell therapy
- multiple myeloma
- regulatory t cells
- stem cells
- clinical trial
- mesenchymal stem cells
- end stage renal disease
- newly diagnosed
- ejection fraction
- induced apoptosis
- chronic kidney disease
- acute lymphoblastic leukemia
- acute myeloid leukemia
- current status
- single cell
- dendritic cells
- cancer therapy
- binding protein
- endoplasmic reticulum stress
- risk assessment
- drug delivery
- oxidative stress
- replacement therapy