Ex vivo gene therapy for malignancies and genetic diseases is time consuming, expensive, and physically taxing on patients, but in vivo alternatives are being developed, and a joint session presented by ASTCT and ASGCT will explore how close to the clinic these new approaches are. Concurrent: Dawn of a New Age?: In Vivo Gene Therap [ASTCT/ASGCT Joint Session] will begin at 10:30 a.m. on Feb. 12 in Ballroom A.

“This session will highlight the complex and complicated way we currently manufacture T cells and stem cells ex vivo in specialized facilities and demonstrate how this can be done directly in patients,” said Session Co-Chair Hans-Peter Kiem, MD, PhD, professor and deputy director of the Translational Science and Therapeutics Division at Fred Hutchinson Cancer Center. “This can be done for both cancer and genetic diseases, so it should be available to a lot more patients.”

Two of the speakers will talk about targeting T cells directly in the patient to treat hematologic or other types of cancer. Andrew Scharenberg, MD, chief executive officer of Umoja Biopharma, will explain in vivo CAR T-cell therapy for hematologic malignancies and autoimmunity. Jennifer Hamilton, PhD, chief scientific officer at Azalea Therapeutics, will discuss cell type-programmable delivery to enable genome engineering in vivo.

The third speaker will describe a non-viral platform that has been used to modify cells directly in animal models and could be beneficial for patients with sickle cell disease or other genetic diseases. Michael Holmes, PhD, chief scientific officer at Tessera Therapeutics, will discuss in vivo genome editing of hematopoietic stem cells (HSCs) and T cells by lipid nanoparticle (LNP) delivery of RNA gene writers.

“In theory, you could genetically change the stem cells of the recipient to whatever you want them to express or delete,” said Session Co-Chair John DiPersio, MD, PhD, the Virginia E. and Sam J. Golman Professor of Medicine at Washington University School of Medicine. “In the case of sickle cell disease, you can change them such that they start increasing fetal hemoglobin, so when they expand enough, the disease will be mitigated.”

DiPersio said the new in vivo technology, which is now in clinical trials, could be paradigm-shifting for gene therapy and must be examined from all angles, including financial costs and durability of treatment compared to ex vivo genetic manipulation and efficacy.

“Everyone who takes care of patients with these malignancies and takes care of patients with inherited diseases of bone marrow should know that these new technologies may be on the horizon and understand their potential for good and their potential for toxicities and risk,” he said. “It sounds very attractive and very exciting, but what are the potential complications? If CAR T cells are generated in vivo, but only 5% of the patients have long-term benefit, then it’s not going to be used, as opposed to ex vivo gene therapy where 40% of the patients are provided long-term benefits.”

This and other sessions at the 2025 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT® and CIBMTR® will be available for on-demand viewing for registered attendees following the live presentation.