Tumor-antigen-specific polyclonal antibodies suppress tumor growth and metastasis in heterogeneous solid tumors
- 1Xenothera , ,
Abstract
Introduction: Tumor heterogeneity and signaling redundancy limit the efficacy of monospecific antibody therapies in solid malignancies. Here we used our platform of glyco-humanized polyclonal antibodies (GH-pAb), to investigate whether targeting multiple tumor-associated antigens provides integrated anti-tumor activity.
Methods: GH-pAb (hereinafter XON7) were generated by immunization of double-knockout pigs with human tumor cells. Antigen specificity of XON7 was assessed using a human proteome array and validated by ELISA. Anti-tumor mechanisms were evaluated in vitro on 2D or 3D-cultures. Efficacy was tested in vivo in cell or patient-derived xenograft (CDX, PDX), in chicken chorioallantoic membrane (CAM) model, and in orthotopic/metastatic triple negative breast cancer (TNBC) models.
Results: XON7 demonstrated tumor-restricted binding across tissue microarrays without detectable staining in matched normal tissues. Mechanistically, XON7 induced potent cytotoxicity across a wide tumor panel through complement activation, apoptosis, and antibody-dependent cellular phagocytosis. Proteome profiling identified predominant reactivities against solute carrier family 3 member 2 (SLC3A2), annexin A2 (ANXA2), and cytoskeleton-associated protein 4 (CKAP4), all broadly expressed tumor-associated surface proteins. Immunodepletion experiments revealed that concurrent targeting of these three targets was required to maintain the full anti-proliferative activity of XON7, supporting a multitarget-dependent mechanism. XON7 also induced released of high-mobility group protein box 1 (HMGB1), a hallmark of immunogenic cell death. In vivo , XON7 inhibited tumor growth in CDX and PDX models, and markedly reduced metastatic dissemination in orthotopic and intravenous TNBC models. In a CAM model, XON7 synergized with PD-1 blockade, enhancing tumor control and promoting macrophage polarization toward a M1 phenotype.
Conclusion: By simultaneously engaging non-redundant tumor pathways and reshaping the tumor microenvironment, XON7 may overcome key resistance mechanisms of solid tumors.
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BibTeX
@article{ciron2026tumorantigenspecific,
title = {{Tumor-antigen-specific polyclonal antibodies suppress tumor growth and metastasis in heterogeneous solid tumors}},
author = {Carine Ciron and Ophélie Dauphouy and Pierre Morice and Pierre-Joseph Royer and Gwenaëlle Evanno and Juliette Rousse and Françoise Shneiker and Bernard Vanhove and Odile Duvaux and Firas Bassissi},
journal = {Frontiers in oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1947593},
url = {https://europepmc.org/article/PMC/PMC13690644},
note = {CC BY},
}
RIS
TY - JOUR
TI - Tumor-antigen-specific polyclonal antibodies suppress tumor growth and metastasis in heterogeneous solid tumors
AU - Carine Ciron
AU - Ophélie Dauphouy
AU - Pierre Morice
AU - Pierre-Joseph Royer
AU - Gwenaëlle Evanno
AU - Juliette Rousse
AU - Françoise Shneiker
AU - Bernard Vanhove
AU - Odile Duvaux
AU - Firas Bassissi
PY - 2026
DA - 2026/10/09
JO - Frontiers in oncology
DO - 10.3389/fonc.2026.1947593
UR - https://europepmc.org/article/PMC/PMC13690644
AB - Introduction: Tumor heterogeneity and signaling redundancy limit the efficacy of monospecific antibody therapies in solid malignancies. Here we used our platform of glyco-humanized polyclonal antibodies (GH-pAb), to investigate whether targeting multiple tumor-associated antigens provides integrated anti-tumor activity. Methods: GH-pAb (hereinafter XON7) were generated by immunization of double-knockout pigs with human tumor cells. Antigen specificity of XON7 was assessed using a human proteome array and validated by ELISA. Anti-tumor mechanisms were evaluated in vitro on 2D or 3D-cultures. Efficacy was tested in vivo in cell or patient-derived xenograft (CDX, PDX), in chicken chorioallantoic membrane (CAM) model, and in orthotopic/metastatic triple negative breast cancer (TNBC) models. Results: XON7 demonstrated tumor-restricted binding across tissue microarrays without detectable staining in matched normal tissues. Mechanistically, XON7 induced potent cytotoxicity across a wide tumor panel through complement activation, apoptosis, and antibody-dependent cellular phagocytosis. Proteome profiling identified predominant reactivities against solute carrier family 3 member 2 (SLC3A2), annexin A2 (ANXA2), and cytoskeleton-associated protein 4 (CKAP4), all broadly expressed tumor-associated surface proteins. Immunodepletion experiments revealed that concurrent targeting of these three targets was required to maintain the full anti-proliferative activity of XON7, supporting a multitarget-dependent mechanism. XON7 also induced released of high-mobility group protein box 1 (HMGB1), a hallmark of immunogenic cell death. In vivo , XON7 inhibited tumor growth in CDX and PDX models, and markedly reduced metastatic dissemination in orthotopic and intravenous TNBC models. In a CAM model, XON7 synergized with PD-1 blockade, enhancing tumor control and promoting macrophage polarization toward a M1 phenotype. Conclusion: By simultaneously engaging non-redundant tumor pathways and reshaping the tumor microenvironment, XON7 may overcome key resistance mechanisms of solid tumors.
SN - 2234-943X
ER -