Engineered human B cells targeting tumor-associated antigens exhibit antigen presentation and antibody-mediated functions
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.
Authors
- Alessio D. Nahmad (ORCID: https://orcid.org/0000-0001-6104-577X)
- Rochelle M. Hinman
- Huseyin Saribasak (ORCID: https://orcid.org/0000-0003-0055-062X)
- Haley Laken
- Alexander A. Boucher (ORCID: https://orcid.org/0009-0004-8212-453X)
- Leah N. Klapper
- Adi Barzel
- Cherylene A. Plewa
- Paula Borden
- Yaron Vagima (ORCID: https://orcid.org/0000-0003-2147-6342)
- Isabella Klooster (ORCID: https://orcid.org/0009-0004-7188-8809)
- Elise Kim
- Natalie Zelikson (ORCID: https://orcid.org/0009-0006-6323-6389)
- Tiansu Wang (ORCID: https://orcid.org/0000-0001-5569-7712)
- Shmuel Hess
- Beenish Khan
- Devin Bridgen
- Jill M. Mooney (ORCID: https://orcid.org/0009-0001-8305-1393)
- Lisa A. Santry
- Courtney Anderson
- Débora Rosa Bublik
- Jeremy Fung
- Cathy Roth
- Michael Vander Oever
- Ana Maria Chadbourne
- Molly Kindschuh
Institutions
- Israel Institute for Biological Research (IL)
- Tel Aviv University (IL)
- United Therapeutics (United States) (US)
- Samueli Institute (US)
- TE Laboratories (Ireland) (IE)
- C4 Therapeutics (United States) (US)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-07-30
- DOI
- https://doi.org/10.3389/fimmu.2025.1621222
- Citations
- 7
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 7.32
Funders
- Horizon 2020 Framework Programme
- HORIZON EUROPE Framework Programme