David Rawlings, MD, on Research That Supports the Development of Engineered B-cell Therapies

“The key advance here is that with that capability, we then can optimize our gene-engineering technology to identify what are the ways to make the cell make the most amount of protein per engineering step. We can use this then to look at our products and make them the most effective possible protein secretors.”

Engineered B-cell therapies are among the emerging therapeutic modalities currently under investigation as a potential alternative to T-cell therapies, such as the chimeric antigen receptor T-cell (CAR-T) therapies that are currently changing the treatment paradigm for some hematological malignancies. This year, at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting, held May 16-20, in Los Angeles, California, members of the labs of David Rawlings, MD, the director of the Center for Immunity and Immunotherapies at Seattle Children's Research Institute; and Richard James, PhD, an associate professor at the University of Washington and a principal investigator at Seattle Children's Research Institute, presented preclinical research on engineered B-cell therapies. The approach involves ex vivo engineering of autologous B-cells to secrete specific therapeutic proteins, after which the B-cells are then infused back into the body with the expectation that they will migrate to and reside in the bone marrow, continuously secreting a substantial amount of the therapeutic protein over a long period of time. Such an application could be used for different types of cancers and other diseases depending on which therapeutic protein the B-cells are engineered to secrete.

In an interview with CGTLive™, held shortly after the meeting, Rawlings discussed some of the main research presented from his lab. In addition to going over the basic design and rationale behind the engineered B-cell therapy approach, Rawlings also spoke about a preclinical study that was conducted with the intention of gaining a better understanding of how the engineered B-cells function. He noted that they intended to address a gap in knowledge about how the RNA expression in the B-cells relates to the amount of therapeutic protein the cells can secrete. With the use of nanocapsule and secretion-sequencing technology, they were able to get a better picture of what is going on at the individual cell level. Rawlings noted that the knowledge gained from this could help to engineer cells that secrete therapeutic protein more effectively. He also touched on a separate relevant preclinical study carried out by Be Biopharma that demonstrated a proof-of-concept for administering engineered B-cells without preconditioning therapy.

REFERENCE
Seattle Children’s Researchers Share Progress at American Society of Gene and Cell Therapy Annual Meeting. Website. Seattle Children’s Research Institute. Accessed October 12, 2023. https://www.seattlechildrens.org/research/featured-research/asgct-2023/