Failure of Rituximab in solid tumors: the tBreg connection

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIA	CANCER-1

Authors

• M Bodogai
• C Lee Chang
• K Wejksza
• J Lai
• M Merino
• AC Chan
• A Biragyn

Abstract

We have previously shown that breast cancer generates regulatory B cells (tBregs) to convert Tregs enabling in this way its metastasis. Thus, we decided to deplete tBregs using aCD20 antibody, a counterpart of the FDA approved strategy for the treatment of B cell malignancies (Rituximab). Unexpectedly, when tumor bearing mice were treated with αCD20 antibody, tumor progression was accelerated leading to increased lung metastasis. Our hypothesis that tBregs may not be targeted by the antibody due to their low expression of CD20 proved to be correct. B cell downregulate their CD20 expression during their conversion to tBregs. Thus, aCD20 antibody treatment in tumor bearing mice leads to the enrichment of tBregs. We provide evidence that CD20 cannot be a target for the depletion of tBregs, explaining the failure of Rituximab to improve clinical outcomes in solid tumors. Instead, we developed an alternative strategy by in vivo targeting CpG through CXCR5 expressed by tBregs. We show that BLCArp-CpG inactivates tBregs, thereby reversing tumor metastasis. Taken together, suppressive B cells need to be controlled in solid tumors.

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