The OX40 protein has the potential to alleviate the main complications of leukemia treatment

Researchers at Baylor College of Medicine and its partner institutions have engineered immune cells to control two major life-threatening complications, graft-versus-host disease (GvHD) and cancer recurrence, which usually occur after
allogeneic hematopoietic stem cell transplantation for leukemia (allo-HSCT).

The findings of the animal model, published in the journal Blood, support further research to determine the feasibility
of using this approach to reduce mortality and improve patient outcomes.

Dr Maksim Mamonkin, assistant professor of pathology and immunology at Baylor University's Center for Cell and Gene Therapy, said: "In general, allogeneic hematopoietic stem cell transplantation is used to treat patients with aggressive diseases that do not respond well to traditional treatments, and it may cure several types of blood cancers
.

Patients first receive intensive chemotherapy, which will eliminate most cancers, but can also severely damage the immune system and hematopoietic cells
.

Transplanted stem cells typically contain a small number of donor immune cells called T cells, which can recognize normal organs and tissues as foreign and initiate an immunorejection-like process
known as graft-versus-host disease (GvHD).

However, immunosuppressive drugs can also hinder a patient's ability to fight infection and cancer, and sometimes don't stop GvHD
.

"This has led us to become interested in finding alternative ways to treat GVHD and tumor recurrence," Mamonkin said
.

The team has accumulated extensive experience in developing engineered T-cell therapies for malignant T cells, such as T-cell leukemia and lymphoma, and testing these methods
in the clinic.

Mamonkin explains: "Our goal is to selectively remove only the T cells that cause GvHD, while maintaining the body's ability to
fight other diseases.

To test this goal, the research team contacted their collaborators at Boston Children's Hospital who studied GvHD
in a non-human primate model.

The researchers then devised a receptor called Allogeneic Immune Defense Receptor (ADR), a molecule they express on therapeutic T cells that enable them to recognize and kill cells
expressing the OX40 protein.

Testing of cells in laboratory and animal models has shown that ADR-armed T cells are very effective at inhibiting T cells mediating GvHD and protecting animals from deadly conditions
.

Inspired by these findings, the team combined leukemia-specific chimeric antigen receptors (CARs) in ADR and T cells to test whether these bibrachial cells could fight cancer recurrence
after both GvHD and HSCT.

Mamonkin said: "We have successfully engineered immune cells from healthy donors to prevent two major causes
of death after bone marrow transplantation.

Engineering T cells to suppress acute GvHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation