ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1621222
This article is part of the Research TopicB-cell Engineering in Malignant and Non-Malignant DiseaseView all articles
Engineered Human B Cells Targeting Tumor-Associated Antigens Exhibit Antigen Presentation and Antibody-Mediated Functions
Provisionally accepted
Alexander Boucher1
Courtney Anderson2Rochelle Hinman2Molly Kindschuh1Jeremy Fung2Tiansu Wang1Isabella Klooster1Elise Kim1Caroline Roth3
Michael Vander Oever3
Bakhmala Khan1Natalie Zelikson4
Yaron Vagima5Huseyin Saribasak1Lisa Santry1Leah Natasha Klapper6Shmulik Hess6
Jill Mooney1
Deby Bublik6Haley Laken2
Adi Barzel7
Philip Borden3Cherylene Plewa1Ana Maria Chadbourne1
Devin Bridgen2
Alessio David Nahmad6,8*- 1ElevateBio, Waltham, United States
- 2Tabby Therapeutics, Watertown, United States
- 3Life Edit Therapeutics, Durham, United States
- 4Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel
- 5Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona, Israel
- 6Tabby Therapeutics, Ness Ziona, Israel
- 7Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
- 8The Samueli Integrative Cancer Pioneering Institute, Petah Tikva, Israel
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B cell engineering represents a promising therapeutic strategy that recapitulates adaptive immune functions, such as memory retention, antibody secretion and affinity maturation in murine models of viral infection. These mechanisms may be equally beneficial in oncology. Recent studies have linked endogenous anti-tumor B cell immunity to favorable prognosis across multiple malignancies. Here, we present functional validation of human B cells engineered to target tumor-associated membrane and intracellular antigens. We demonstrate that engineered B cells express therapeutically relevant membrane B cell receptors that are secreted as antibodies upon differentiation. Additionally, engineered B cells take up tumor-associated antigens and demonstrate potent antigen presentation capabilities, while their secreted antibodies activate T cell responses via immune complexes and induce tumor-directed cytotoxic responses. B cell engineering to target tumor-associated antigens may thus have utility as a novel modality for solid tumor therapy.
Keywords: antibody, B cell, Tertiary lymphoid structure (TLS), immune complex, Antigen Presentation, Genome editing, Cell Engineering
Received: 30 Apr 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Boucher, Anderson, Hinman, Kindschuh, Fung, Wang, Klooster, Kim, Roth, Vander Oever, Khan, Zelikson, Vagima, Saribasak, Santry, Klapper, Hess, Mooney, Bublik, Laken, Barzel, Borden, Plewa, Chadbourne, Bridgen and Nahmad. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alessio David Nahmad, The Samueli Integrative Cancer Pioneering Institute, Petah Tikva, Israel
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