ID #238 Engineered plasma B cells as a targeted cellular immunotherapy against diffuse intrinsic pontine glioma

Abstract

Targeted cellular immunotherapies hold promise against pediatric brain tumors, evidenced by the preliminary efficacy of B7-H3- and GD2-targeting CAR T cells against DIPG. However, benefit was not universal, underscoring the need to further explore therapies capable of more durable treatment responses. While most cellular therapy advancements have centered on T cells, B cells are an attractive engineered option to design in vivo antibody production centers. In fact, B cells can be designed to secrete specific tumor-targeting antibodies and to initiate anti-tumor immune responses. Here, we engineered anti-GD2 antibody-producing B cells as a novel targeted immunotherapeutic approach against DIPG. Early data demonstrates functionality of the modified B cells, confirming cells were successfully engineered to produce anti-GD2 antibodies. In vitro affinity testing shows that anti-GD2 antibodies from engineered B cells binds to GD2 protein on DIPG cultures as well as commercially available anti-GD2 antibodies. In vivo, we have supporting data showing that the engineered human plasma B cells can be injected via ICV into the brains of NSG mice where they persist for over a week post-injection and, critically, secrete anti-GD2 antibodies. More importantly, immunostaining of treated mice indicates elevated immune cell recruitment to sites of anti-GD2 antibody secretion. These results represent the first foundational preclinical attempts to use engineered B cells secreting tumor-targeted antibodies against pediatric brain tumors and specifically validate the potential of anti-GD2 antibody secretion which is now in in vitro efficacy studies.