On May 19, 2023 Be Biopharma, Inc. ("Be Bio"), a company pioneering the discovery and development of Engineered B Cell Medicines (BeCMs), reported that it will present first-of-its-kind preclinical research today from a collaboration study showing homing and engraftment of B cells in non-human primates (NHPs) with intact immune systems (Press release, Be Biopharma, MAY 19, 2023, View Source [SID1234631880]). The findings will be presented during a late-breaking oral presentation at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 26th Annual Meeting from 9:30-9:45 a.m. PST. The study was funded and conducted through a collaborative research and development agreement with the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

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The study was designed to evaluate engraftment without preconditioning of ex vivo expanded NHP plasma cells. Plasma cells are terminally differentiated B cells which can live for decades1 and have the capacity to secrete extremely high levels of protein2. In two NHPs, B cells were collected, expanded, and differentiated into plasma cells. The resulting cells were radiolabeled and directly infused into the NHPs and tracked by PET imaging. Rapid homing (within one hour) and engraftment to plasma cell niches in the bone marrow and spleen were observed with a consistent signal over a six-day period. Radiolabeled cells were also observed in the liver. Greater than 20% of the total cells dosed engrafted into the plasma cell niche by day one and high-resolution imaging of the bone marrow compartment showed cellular distribution comparable to human bone marrow. No toxicities in the study were identified.

"NHP engraftment without preconditioning validates a key pillar of the Be Bio platform and broadens the potential clinical utility of engineered B cell medicines for patients where preconditioning toxicities are unacceptable or outweigh therapeutic benefit," said Dr. Rick Morgan, Chief Scientific Officer, Be Bio. "Be Bio’s stable engineering platform for the expression of diverse therapeutic proteins by engineered B cells represents a promising approach for a new class of medicines with broad therapeutic utility."

"NHPs with intact immune systems have close similarities to humans and can model autologous and allogeneic cell therapy treatment," said Dr. David Young, Staff Clinician, Translational Stem Cell Biology Branch, NHLBI. "Our results show for the first time that ex vivo expanded plasma cells distribute to the bone marrow and spleen in patterns comparable to human sites of active blood cell formation."

In the next phase of the study, long-term engraftment without preconditioning and tracking of BeCMs are planned in NHPs with intact immune systems.

Study Design

Peripheral blood B cells were collected and purified from two adult rhesus monkeys (12 and 10 years old) and expanded over eight days in a defined serum-free culture to yield ≥10-fold expansion (measured by live cell count) with a final viability of ≥80% (measured by percent of live cells). Differentiation to plasma cells was demonstrated by loss of CD20 (protein found in B cells) along with antibody class switching (>75% Immunoglobulin G producing cells). The plasma cell product was radiolabeled with zirconium-89-oxine and intravenously infused. Imaging was performed using high sensitivity PET/CT tracking of the BeCMs. PET/CT images were acquired at 15 minutes, one hour and then one, three and six-days post-infusion.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

About B Cells – A New Class of Cellular Medicines

Imagine what could "Be?" In nature, a single B cell engrafts in the bone marrow and can produce thousands of proteins per second at constant levels over decades. B cells are nature’s exquisite medicine factories, manufacturing proteins to fight disease and maintain health. Unleashing the power of B cells is driving a new class of cellular medicines – Engineered B Cell Medicines (BeCMs). BeCMs have the potential to be durable, allogeneic, redosable and administered without toxic conditioning. The promise of BeCMs could transform therapeutic biologics with broad application — across protein classes, patient populations and therapeutic areas.