Cancer Immunotherapy Based on Engineered Immune Cells as a Promising Approach Against Myeloma

Cancer Immunotherapy Based on Engineered Immune Cells as a Promising Approach Against Myeloma

A study recently published in the journal Nature Medicine revealed that cancer immunotherapy can be successfully employed against multiple myeloma. The study is entitled “NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma” and was led by researchers at the University of Maryland School of Medicine, the Perelman School of Medicine at the University of Pennsylvania and the biopharmaceutical company Adaptimmune.

Myeloma is a type of cancer that develops from cells in the bone marrow called plasma cells. Since plasma cells are present in several places in the body, the disease is often referred to as multiple myeloma. It is estimated that more than 77,000 individuals in the United States have multiple myeloma, with approximately 24,000 new cases diagnosed every year. Myeloma patients are often treated with chemotherapy and also autologous stem cell transplant; however, the long-term response rates are low and the median survival is estimated to be three to five years. Multiple myeloma remains a condition largely incurable.

Cancer immunotherapy is defined by the use of the body’s own immune system to help fight cancer, and it has emerged in recent years as a promising therapy for certain cancers. In the study, the team investigated whether immunotherapy can also be applied in multiple myeloma cases.

The team conducted a phase I/II trial to assess the safety and efficacy of autologous T cells (important immune cells) that were engineered to express an affinity-enhanced T cell receptor (TCR) that recognizes the specific cancer antigens NY-ESO-1 and LAGE-1. Up to 60% of advanced myelomas express NY-ESO-1 and/or LAGE-1, antigens that are linked to cancer proliferation and poorer outcomes. In total, 20 patients with advanced myeloma were given autologous engineered T cells.

Researchers reported that T cell infusions were well tolerated and that these engineered T cells were able to expand, persist in the blood and traffic into the marrow where they had a cytotoxic phenotype fighting the malignant cells. The team found that the persistence of engineered T cells in the patient’s blood was inversely correlated to the levels of NY-ESO-1 in the marrow, whereas the loss of T cell persistence resulted in disease progression or relapse. 80% of the patients had a positive clinical response to the therapy with 70% (14 patients) having a near complete or complete response and 10% (2 patients) having very good partial response three months after treatment. The median progression-free survival was of 19.1 months.

The research team concluded that TCR–engineered T cells recognizing myeloma antigens NY-ESO-1 and LAGE-1 is overall a safe and well-tolerated therapeutic strategy that can interfere with myeloma progression.

“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,” said the study’s lead author Dr. Aaron P. Rapoport from the University of Maryland School of Medicine in a news release. “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.”

Genetically modified T-cells have been previously used as a treatment strategy for leukemia and lymphoma, but this clinical trial is the first published report of their use against multiple myeloma.

“The majority of patients who participated in this trial had a meaningful degree of clinical benefit,” stated Dr. Rapoport. “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.”

“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,” added the dean of the University of Maryland School of Medicine Dr. E. Albert Reece. “This trial is also an excellent example of significant scientific advances that result from collaborations between academic medical institutions and private industry.”