B Cell-Based Cancer Immunotherapy

Abstract

B cells are not only producers of antibodies, but also contribute to immune regulation or act as potent antigen-presenting cells. The potential of B cells for cellular therapy is still largely underestimated, despite their multiple diverse effector functions. The CD40L/CD40 signaling pathway is the most potent activator of antigen presentation capacity in B lymphocytes. CD40-activated B cells are potent antigen-presenting cells that induce specific T-cell responses in vitro and in vivo. In preclinical cancer models in mice and dogs, CD40-activated B cell-based cancer immunotherapy was able to induce effective antitumor immunity. So far, there have been only few early-stage clinical studies involving B cell-based cancer vaccines. These trials indicate that B cell-based immunotherapy is generally safe and associated with little toxicity. Furthermore, these studies suggest that B-cell immunotherapy can elicit antitumor T-cell responses. Alongside the recent advances in cellular therapies in general, major obstacles for generation of good manufacturing practice-manufactured B-cell immunotherapies have been overcome. Thus, a first clinical trial involving CD40-activated B cells might be in reach.

Keywords: Antigen presentation; B-cell therapy; Cellular therapy.

Fig. 1

Concept of a possible CD40B-cell study. B cells can be isolated from tumor-infiltrating lymphocyte tumors (TIL) or alternatively from peripheral blood (1) by CD19 microbeads (2). After cultivation and expansion in the CD40L culture (3), the activation status is checked by determining the expression of the activation markers, CD80, CD86, MHC class I, and MHC class I, which are usually highly upregulated after CD40L stimulation (4). After pulsing with a suitable tumor antigen (5), CD40B cells are reinjected into the patient (6).