Cellular therapy a new tool for treating cancer, autoimmune diseases

Michael C. Milone, MD, PhD: “One way of thinking about the therapies we’re making is that we are engineering T-cells with portions of antibodies derived to get the specificity of that antibody. Then we use the T-cell machinery, which is a potent killing machine.”

Adoptive cellular therapy is a promising platform for treating cancers using genetically engineered T-cells to target B-cells linked to a disease. The technology is now being used to target cells that cause the autoimmune blistering disease pemphigus vulgaris.

Michael C. Milone, MD, PhD, a pioneer in the use of adoptive cellular therapy, explained how it works and how close researchers are to using it to treat pemphigus vulgaris Friday during his Plenary presentation, “Genetically Engineered T-Cell Therapy for B-Cell Mediated Diseases.”

“A potent killing machine”

“One way of thinking about the therapies we’re making is that we are engineering T-cells with portions of antibodies derived to get the specificity of that antibody. Then we use the T-cell machinery, which is a potent killing machine. We engage that through an artificial synthetic receptor known as a CAR,” Dr. Milone said in an interview about his presentation.

A CAR — a chimeric antigen receptor — is an artificial receptor used to direct an engineered T-cell toward another cell, such as a B-cell. The first commercially developed CARs target the CD19 molecule on normal and malignant B-cells. Two of these therapies, CTL019, also known as tisagenlecleucel-T, and KTE-C19, also known as axicabtagene ciloleucel, are currently under regulatory review by the FDA for the treatment of acute lymphoblastic leukemia and lymphoma, he said.

Potential treatments

These CAR T-cell therapies could potentially be used to treat autoimmune diseases, said Dr. Milone, who is an associate professor of pathology and laboratory medicine at the Hospital of the University of Pennsylvania. He also is an investigator in the Center for Cellular Immunotherapies at the University of Pennsylvania Perelman School of Medicine.

Dr. Milone compared CTL019 to the monoclonal antibody rituximab, which targets CD20, another molecule on B-cells. “It is kind of a continuous rituximab. It continuously targets its antigen as long as those T-cells persist.”

Adoptive cellular therapy is now being used to develop a treatment for pemphigus vulgaris. It targets the specific B-cells that make antibodies to desmoglein molecules rather than all B-cells, which are eliminated by drugs such as rituximab or CTL019.

“Desmoglein molecules are part of the ‘glue’ that holds cells in your skin together,” Dr. Milone said. “When your body makes these antibodies, you disrupt the junctions between cells and you get blisters. It is a very specific disease caused by these antibodies.

“If we take away these antibodies by a procedure that takes out blood, removes the serum, and replaces it — a procedure called plasma exchange or plasmapheresis — these patients often respond to that therapy.”

Future encouraging for cellular therapy

Dr. Milone and a team of University of Pennsylvania researchers, which includes dermatologist Aimee Payne, MD, PhD, are completing preclinical work on the therapy. It targets the autoimmune B-cells making antibodies to desmoglein 1 and desmoglein 3 in pemphigus. He said researchers hope to soon be able to start a phase 1 clinical trial to test the treatment.

“Cellular therapy for cancer was recently approved by the FDA,” Dr. Milone said. “It is on the verge of becoming a standard of care for patients with leukemia and lymphomas. It is possible to think about how we might apply these technologies to patients with autoimmune-mediated disease, particularly those with B-cell mediated diseases.”

Return to AAD Daily articles

Top