Multiple myeloma is a blood cancer caused by plasma cells and remains a medical challenge as existing treatments fail to produce lasting treatments. Newer targeted therapies involve adding a protein called chimeric antigen receptor (CAR) to immune cells called T cells (CAR-T). The current FDA has approved CAR-T products for myeloma target BCMA, which is expressed on most myeloma cells and only on certain normal B cells and plasma cells, making it a good protein target. BCMA cars expressing T cells (BCMA CAR-T) are redirected to bind and kill BCMA-expressing myeloma cells. Although most patients respond to BCMA CAR-T, they eventually relapse. In addition, CAR-T cells can cause cytokine release syndrome (CRS) and neurological toxicity, which may be mild moderate or severe side effects of CAR-T treatment on myeloma. However, a new approach: adding BCMA cars to different dedicated immune cells called invariant natural T cells (Inkt; BCMA Car-Inkt) and combining treatment of long-acting IL-7 molecules to improve their effectiveness sex, which shows encouraging results in recent studies.
Professors Julie O’Neal and John Dipersio of the University of Washington recently published their blood progress study. Treated alone or in combination with long-acting IL-7 molecules using BCMA CAR-INKT cells, these mice were implanted with multiple myeloma tumor cells expressing BCMA. They showed that IL-7 enhanced the swelling and durability of mouse BCMA CAR-INKT cells and provided better tumor control than mice treated with BCMA CAR-INKT cells alone.
To address the safety of this new therapy, the team compared the potential of CAR-INKT to induce CRS. In these studies, they used an assay developed in the laboratory that measured IL secretion of immature dendritic cells in the context of tumor killing by BCMA CAR-T or BCMA CAR-INKT effector cells 6. They saw a trend toward lower IL-6 secretion caused by Car-Inkt compared with CAR-T known to induce CR. As O’Neal reported, these findings are promising: “Car-Inkt cells may cause fewer or more severe CR in human patients, and if so, it may be the use of CAR-INKT instead of CAR- Advantages of T cells.”
In summary, this study offers exciting new possibilities for the treatment of multiple myeloma, providing alternatives to existing therapies. An innovative combination of CAR-INKT cells with IL-7 exhibits anti-fibroid activity and may have safer characteristics. The authors noted that further research is planned to continue to develop and improve CAR-INKT treatment for the treatment of multiple myeloma.
Journal Reference
O’Neal J, Cooper ML, Ritchey JK, Gladney S, Niswonger J, GonzálezLS, Street E, Haas GJ, Carter A, Amayta PN, Gao F, Gao F, Lee BH, Choi BH, Choi D, Berrien-Elliott M , Berrien-Elliott M, fehhou A, Fehniger, Fehniger, Fehniger, Fehniger, Fehniger, Fehniger TA, Rettig MP, Dipersio JF. Long-acting IL-7, RHIL-7-HYFC enhances the anti-fibroid efficacy of CAR-INKT. Adverb of blood. October 24, 2023; 7 (20): 6009-6022. doi: https://doi.org/10.1182/bloodadvances.2023010032.
About the Author
Dr. Julie O’Neal He is an assistant professor of medicine at Washington University in St. Louis and leads the Translation Multiple Myeloma Immunotherapy Program in John Dipersio’s lab. Her research includes designing novel single and dual-target chimeric antigen receptors (CAR), and expressing them on T (CAR-T) or Inkt (Car-Inkt) cells, and preclinical in vitro and in vivo myeloma models Test it in . She is also testing the effects that will enhance the durability and efficacy of modified immune cells to improve their activity. Finally, efforts are being made to use proteomics and genetics to better understand the basic biology of automotive proteins and Inkt cells.
Dr. John Diperso, MD He is a Virginia E and Sam J. Gorman professor of medicine at Washington University School of Medicine in St. Louis, Gene and director of the Center for Cell Immunotherapy. His research focuses on the basic and transformational aspects of leukemia, lymphoma and stem cell biology. These studies include identifying genetic abnormalities in human leukemia and understanding processes involving stem and leukemia cell trafficking and clinical and transformational procedures for two leukemia/MD.
Featured Image Source:
Dr. Erhabor Osaro, CC BY-SA 3.0, via Wikimedia Commons
