Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Between symbolism and incrementalism : moving forward with the gender equality project in Poland

The purpose of this paper is to examine whether the recently adopted law on gender electoral quotas marks a change in the approach to gender issues and gender equality in Poland. It also aims to describe the trajectory of women’s movement in a post-Communist country and to identify causes related to the role of women in the Solidarity movement that resulted in low visibility of women in government and decision-making positions. The paper departs from the assumption that Poland is not moving away from a narrowly conceived equal rights/opportunities model, because such model has not yet been fully implemented. In the context of the present ‘war on gender’, women’s full political, economic, social, and more specifically, private citizenship is a long-term project. As of now, women remain instrumental for achieving political parties’ further aims, and any gestures that seem to advance women’s position in the public sphere are usually merely symbolic. Yet, the emergence of a strong women’s movement helps to frame the public discourse in gendered terms and gradually include its propositions in the mainstream policy