ArticleCancer cell international2019
AGI-134: a fully synthetic α-Gal glycolipid that converts tumors into in situ autologous vaccines, induces anti-tumor immunity and is synergistic with an anti-PD-1 antibody in mouse melanoma models.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Arming Inactivated Enveloped Virus Vaccines with theVaccines · 2026Review
- The α-Gal Epitope (Galα1-3Galβ1-4GlcNAc) as Therapeutic Agent in Cancer Immunotherapy, Vaccine Effectiveness Amplification and Injured Tissue Regeneration.International journal of molecular sciences · 2026Review
- Lessons of Macrophage-Associated Heart Regeneration in Fish, Amphibians, and Neonatal Mice, Applied to Adult Mice: A Perspective on α-Gal Nanoparticles.International journal of molecular sciences · 2026Review
- Sociodemographic determinants and assessment of anti-α-Gal IgG titers in head and neck cancer patients.Frontiers in oncology · 2025Article
- Self-Tumor Antigens in Solid Tumors Turned into Vaccines by α-gal Micelle Immunotherapy.Pharmaceutics · 2024Review
- Regeneration in Mice of Injured Skin, Heart, and Spinal Cord by α-Gal Nanoparticles Recapitulates Regeneration in Amphibians.Nanomaterials (Basel, Switzerland) · 2024Review
- Antibody production and tolerance to the α-gal epitope as models for understanding and preventing the immune response to incompatible ABO carbohydrate antigens and for α-gal therapies.Frontiers in molecular biosciences · 2023Review
- Neoantigens and their potential applications in tumor immunotherapy.Oncology letters · 2022Review
- Secreted phosphoprotein 1 as a potential prognostic and immunotherapy biomarker in multiple human cancers.Bioengineered · 2022Article
- Live unattenuated vaccines for controlling viral diseases, including COVID-19.Journal of medical virology · 2021Review
- Biosynthesis of α-Gal Epitopes (Galα1-3Galβ1-4GlcNAc-R) and Their Unique Potential in Future α-Gal Therapies.Frontiers in molecular biosciences · 2021Review
- Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives.British journal of cancer · 2020Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTreatments that generate T cell-mediated immunity to a patient's unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualized ex vivo processing or manufacturing processes are especially sought after. Here we report that AGI-134, a glycolipid-like small molecule, can be used for coating tumor cells with the xenoantigen Galα1-3Galβ1-4GlcNAc (α-Gal) in situ leading to opsonization with pre-existing natural anti-α-Gal antibodies (in short anti-Gal), which triggers immune cascades resulting in T cell mediated anti-tumor immunity.
methodsVarious immunological effects of coating tumor cells with α-Gal via AGI-134 in vitro were measured by flow cytometry: (1) opsonization with anti-Gal and complement, (2) antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells, and (3) phagocytosis and antigen cross-presentation by antigen presenting cells (APCs). A viability kit was used to test AGI-134 mediated complement dependent cytotoxicity (CDC) in cancer cells. The anti-tumoral activity of AGI-134 alone or in combination with an anti-programmed death-1 (anti-PD-1) antibody was tested in melanoma models in anti-Gal expressing galactosyltransferase knockout (α1,3GT
resultsIn vitro, α-Gal labelling of tumor cells via AGI-134 incorporation into the cell membrane leads to anti-Gal binding and complement activation. Through the effects of complement and ADCC, tumor cells are lysed and tumor antigen uptake by APCs increased. Antigen associated with lysed cells is cross-presented by CD8α+ dendritic cells leading to activation of antigen-specific CD8+ T cells. In B16-F10 or JB/RH melanoma models in α1,3GT
conclusionsWe have identified AGI-134 as an immunotherapeutic drug candidate, which could be an excellent combination partner for anti-PD-1 therapy, by facilitating tumor antigen processing and increasing the repertoire of tumor-specific T cells prior to anti-PD-1 treatment.
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