In cellular immunotherapy, healthy T cells (above) are removed from patients, genetically engineered to target their cancer, and injected back into the body. [NIAID]
In cellular immunotherapy, healthy T cells (above) are removed from patients, genetically engineered to target their cancer, and injected back into the body. [NIAID]

Stimulating a patients’ immune system to combat diseases like cancer lies at the heart of immunotherapy and in recent years it has emerged as one of the most promising treatment options. Now, a clinical study from University of Maryland School of Medicine, the Perelman School of Medicine at the University of Pennsylvania, and Adaptimmune, a clinical-stage biopharmaceutical company, has published data that shows significant success using this technique against multiple myeloma.  

Typically, immunotherapies fall into one of three categories: cytokine, antibody, and cellular. Cytokine treatments have been administered for various cancers and attempt to modulate the immune response toward the disease and have been modestly successful. Antibody therapies have shown great promise for a variety of cancers and have become the focus of many biopharmaceutical companies of the past several years. These molecules bind to the target antigen on the cell surface, marking it for destruction by the immune system.

Cellular therapies have been slow to make their way into the clinical realm as the method has been wrought with an array of technical difficulties. However, recent advances in sequencing and genome editing tools have enabled researchers to engineer a patients’ own immune cells to target specific tumor subtypes—multiple myeloma in the case of the current clinical trial.      

“This study suggests that treatment with engineered T cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma,” explained lead author Aaron Rapoport, M.D., professor of medical oncology at the University of Maryland School of Medicine. “Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients.”

The findings from this study were published recently in Nature Medicine through an article entitled “NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma.”

More than 24,000 new cases of multiple myeloma are diagnosed each year, with long-term response rates being extremely low and median survival rates of three to five years.

“The majority of patients who participated in this trial had a meaningful degree of clinical benefit,” Dr. Rapoport noted. “Even patients who later relapsed after achieving a complete response to treatment or didn't have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly three years.”

In this study, patients' T cells were engineered to express an affinity enhanced T cell receptor, specific for the tumor antigens known as NY-ESO-1 and LAGE-1. Close to 60% of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1—correlating to tumor proliferation and poorer outcomes.

In the current study, 20 patients were treated using cell immunotherapy, of which 14 (70%) had a near complete or complete response after three months. Median progression-free survival was 19.1 months and overall survival was 32.1 months. Additionally, the researchers found that the engineered T-cells were migrating to their intended target zone within the bone marrow and showed persistence that correlated with clinical activity against antigen-positive myeloma.

“Multiple myeloma is a treatable but largely incurable cancer. This study reveals the promise that immunotherapy with genetically engineered T-cells holds for boosting the body's ability to attack the cancer and provide patients with better treatments and control of their disease,” stated E. Albert Reece, M.D., Ph.D., M.B.A., dean of the University of Maryland School of Medicine, who wasn’t directly involved in the current study. “This trial is also an excellent example of significant scientific advances that result from collaborations between academic medical institutions and private industry.”

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