AUTHOR=Guberman Bracha Michal , Biber Guy , Zelikson Natalie , Shavit Sharon , Avraham Roy , Vagima Yaron , Bublik Débora Rosa , Katz Yael , Barzel Adi , Klapper Leah Natasha , Hess Shmuel , Nahmad Alessio David TITLE=Mouse B cells engineered to express an anti-HPV antibody elicit anti-tumor T cell responses JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1613879 DOI=10.3389/fimmu.2025.1613879 ISSN=1664-3224 ABSTRACT=Transplantation of engineered B cells has demonstrated efficacy in HIV disease models. B cell engineering may also be utilized for the treatment of cancer. Recent studies have highlighted that B cell activity is associated with favorable clinical outcomes in oncology. In mice, polyclonal B cells have been shown to elicit anti-cancer responses. As a potential novel cell therapy, we demonstrate that engineering B cells to target a tumor-associated antigen enhances polyclonal anti-tumor responses. We observe that engineered B cells expressing an anti-HPV B cell receptor internalize the antigen, enabling subsequent activation of oncoantigen-specific T cells. Secreted antibodies from engineered B cells form immune complexes, which are taken up by antigen-presenting cells to further promote T cell activation. Engineered B cells hold promise as novel, multi-modal cell therapies and open new avenues in solid tumor targeting.