Inducible B effector cells (iBECs) for cancer immunotherapy (46.4)

Abstract

Abstract While cellular immunotherapy for malignances has traditionally focused on the development and manipulation of tumor targeted DCs, T and NK cells, B cells have remained vastly underutilized as a potential source for adoptive cell therapy. Here we demonstrate that B cells stimulated with FIST-2, a novel chimeric protein consisting of IL-2 fused to the ectodomain of the TGFβ receptor (type II), can adopt an effector phenotype with potent antitumor activity. Treatment with FIST-2 induces naïve splenic B cells to become B effector cells (iBECs), characterized by hyperphosphorylation of STAT3 and 5 downstream of the IL-2 receptor, upregulation of transcription factor, T-bet, and secretion of pro-inflammatory cytokines: IFNγ, TNFα and IL-6. iBECs retained their B cell identity by CD19 and PAX5 expression, but adopted an enhanced APC phenotype through upregulation of cell surface markers associated with antigen presentation and co-stimulation, including: MHC-II, CD80 and CD86. To determine whether iBECs conferred antitumor immunity, we utilized a mouse model of lymphoma expressing ovalbumin (EG.7-OVA). Syngeneic iBECs pulsed with OVA were able to activate OVA-specific OT-I and OT-II T cells in vitro, suggesting that they act as APCs. In vivo administration of OVA-pulsed iBECs protected immunocompetent C57BL/6 mice from EG.7-OVA tumor challenge, and promoted tumor regression in mice with pre-established tumors. These data support the concept of B cell-based adoptive immunotherapy.