New study investigates BAFF CAR T-cell therapy in relapsed myeloma

Hematologist and oncologist Leland Metheny, MD, of the University Hospitals (UH) Seidman Cancer Center is leading the study. He says in the two years since completing basic preclinical work, the team has shown that it is possible to create BAFF CAR T cells for human subjects. The innovation is to introduce genes into T cells through the process of electroporation at the Wesley Center for Immunotherapy at the UH Seidman Cancer Center.

In January 2022, a research team from UH Seidman Cancer Center and Case Western Reserve University published a groundbreaking report in the journal Nature Communications describing a novel approach to chimeric antigen receptor (CAR) T-cell therapy for B-cell cancer. The new B-cell activating factor (BAFF) CAR-T product, developed by scientist Reshmi Parameswaran, MS, PhD, and colleagues at UH Seidman Cancer Center and Case Western Reserve University, specifically binds to each of three receptors rather than one—BAFF-R, BCMA, and TACI—providing more therapeutic options and avoiding the problem of antigen escape currently seen with CAR-T therapies that target CD19 exclusively. Experimental results demonstrated that BAFF CAR T can effectively kill multiple B cell cancers, with BAFF CAR T cells exerting robust in vitro and in vivo cytotoxicity against mantle cell lymphoma, multiple myeloma and acute lymphocytic leukemia xenograft mouse models.

Now, just two short years later, these pivotal findings form the basis for the BAFF CAR T Phase I clinical trial for patients with relapsed and refractory multiple myeloma.

The new multiple myeloma trial at UH Seidman will enroll up to 20 patients with relapsed or refractory myeloma and three or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.

“Our study will establish a safe dosing regimen and provide an initial signal of BAFF CAR T cell activity against relapsed myeloma. We will use a manufacturing process that could be replicated in multiple academic institutions with the appropriate cellular manufacturing facilities,” says Dr. Metheny.

The primary objective is to determine the maximum tolerated and recommended dose of BAFF CAR T cells for a Phase II trial. Secondary objectives include determining the toxicity profile, objective response rate, complete response rate, duration of response, progression-free survival, overall survival, incidence of side effects, and incidence of antibodies to the BAFF CAR T cells. Dr. Metheny and team will collect data over a 24-month period.

Dr. Metheny says he is excited about the potential for the patients he treats.

“There is a continuing need to develop new, effective therapies to treat myeloma,” he says. CAR-T cell therapy has been shown to be effective against refractory myeloma. With this study, we are testing whether BAFF-CAR-T cells can provide another strategy for our patients with refractory disease.”

The study is being conducted under an agreement between University Hospitals and Luminary Therapeutics, a biotech startup based in Minneapolis. Luminary is a company developing allogeneic CAR-T drugs and has programs to treat B-cell malignancies, autoimmune diseases and solid tumors.