Researchers at Mayo Clinic Cancer Center are studying a potential new chimeric antigen receptor-T cell therapy (CAR-T cell therapy) treatment for multiple myeloma. Their findings were published on Friday, June 24, in The Lancet.

"CAR-T cell therapy is a type of immunotherapy that involves harnessing the power of a person's own immune system by engineering their T cells to recognize and destroy cancer cells," says Yi Lin, M.D., a Mayo Clinic hematologist and lead author of the study.

Dr. Lin says the Food and Drug Administration approved idecabtagene vicleucel, the first CAR-T cell treatment for multiple myeloma, in March. "Today, we are working toward another potential CAR-T cell treatment for multiple myeloma," says Dr. Lin.

Dr. Lin says the CARTITUDE-1 study is a registration-phase 1B/II clinical trial. The trial tested B cell maturation antigen targeting CAR-T cell therapy, ciltacabtagene autoleucel (cilta-cel), in patients with multiple myeloma who received at least three previous lines of therapy with standard drugs, including proteasome inhibitors, immunomodulatory drugs and CD38 antibodies.

Dr. Lin says the overall response rate to the treatment was 97%, while the complete response rate and progression-free survival rates were 67% and 77%, respectively. The overall survival rate was 89%.

"Updates on this study were also recently presented at the American Society of Clinical Oncology annual meeting, which occurred after our paper was accepted for publication in The Lancet," says Dr. Lin. "Our ASCO presentation showed a continued deepening response for patients receiving this therapy, with a complete response rate of 80%," says Dr. Lin. "These are very impressive results for myeloma patients who have already gone through many lines of therapy for their disease."

By cleavage with enzyme papain, the Fab (fragment-antigen binding) part can be separated from the Fc (fragment crystalline) part of the molecule. The Fab fragments contain the variable domains, which consist of three hypervariable amino acid domains responsible for the antibody specificity embedded into constant regions.

There are four known IgG subclasses all of which are involved in Antibody-dependent cellular cytotoxicity. The immune system responds to the environmental factors it encounters on the basis of discrimination between self and non-self.  Tumor cells are not specifically targeted by one's immune system since tumor cells are the patient's own cells. Tumor cells, however are highly abnormal, and many display unusual antigens that are either inappropriate for the cell type, its environment, or are only normally present during the organisms' development (e.g. fetal antigens).

Examples include ErbB2, a constitutively active cell surface receptor that is produced at abnormally high levels on the surface of approximately 30% of breast cancer tumor cells. Such breast cancer is known a HER2 positive breast cancer. Antibodies are a key component of the adaptive immune response, playing a central role in both in the recognition of foreign antigens and the stimulation of an immune response to them. The advent of monoclonal antibody technology has made it possible to raise antibodies against specific antigens presented on the surfaces of tumors.

Going forward, Dr. Lin says it will be important to better understand the clinical features of patients who have experienced durable remissions on this therapy and the mechanisms behind patients who relapse. "While comparisons cannot be formally made across two separate single-arm studies of ide-cel and cilta-cel, the impressive high response rate and progression-free survival of patients treated with cilta-cel are very exciting," says Dr. Lin. She cautions, however, that the potential translation of this research into a clinical individualized therapy will require solving many logistical details, including ensuring that the transition from manufacturing for research to a commercial product remains reliable.

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