New Ways to Fight Infection in Transplant Recipients

Pawel Muranski

An immunologist and his colleagues at Columbia’s Cellular Immunotherapy Laboratory have developed a “living drug,” an experimental cell therapy that offers new options to prevent viral infections in organ and bone marrow transplant patients.

Pawel Muranski, MD, director of the Cellular Immunotherapy Laboratory, saw the need for such cells when he worked at the NIH, where some of the original immunotherapy strategies were developed. He was part of an NIH team that developed a way to produce large numbers of virus-specific T cells trained to identify and safely eliminate a patient’s viral infection without affecting the patient’s vital organs.

The approach focuses on transplant patients and their suppressed immune systems.

“The idea behind our cell therapy is that we can take T cells from a healthy donor, select the ones that recognize the virus, and multiply those in the lab so we create a population of immune cells that we can give to the patient to control the infection,” says Dr. Muranski, assistant professor of medicine and of pathology & cell biology and a principal investigator at Columbia’s Center for Translational Immunology.

At the NIH, however, growing the cells took weeks, too long to be helpful in fighting virulent infections. At Columbia, Dr. Muranski and his team created a faster technique that requires only a small blood sample from the donor. As of late October, three patients had received the cell therapy without any adverse reactions, and several other patients have been enrolled in a phase 1 clinical trial that is testing the therapy’s safety. Once the phase 1 safety study is completed, the therapy’s effect will be rigorously tested in a phase 2 trial, when multiple doses of cells may be used to increase the odds of effectiveness.

Dr. Muranski’s next target is to develop a new type of T-cell therapy to attack cancer. Currently available CAR-T cells (T cells from patients that are genetically engineered to recognize cancer) have shown great success in patients with certain blood cancers but as of now have not been successful in patients with common solid cancers. Naturally occurring T cells known as tumor-infiltrating lymphocytes (or TILs) have shown great promise in patients with certain cancers, says Dr. Muranski.

He focuses on a type of T cell called CD4+ T-helper cells that are master orchestrators of the entire immune system, and his laboratory is generating them from peripheral blood of patients. Dr. Muranski’s cell production facility, which opened in 2022, supports the development of other in-house cell therapies.

“Many immunotherapies originate at academic institutions and then are developed further by industry,” says Dr. Muranski. “With academic cell manufacturing, we can easily and rapidly translate new ideas for therapies into early phase clinical trials and see if they are safe and effective. “We’re not trying to replicate what industry is doing,” he adds. “The idea is to innovate and produce the next generation of cell therapies.”