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Characterization of a neutralizing anti-human galectin-1 monoclonal antibody with angioregulatory and immunomodulatory activities

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Abstract

Galectins, a family of highly conserved β-galactoside-binding proteins, control tumor progression by modulating different hallmarks of cancer. Galectin-1 (Gal-1), a proto-type member of this family, plays essential roles in tumor angiogenesis and immunosuppression by cross-linking glycosylated receptors on the surface of endothelial and immune cells. Targeted disruption of Gal-1 suppresses tumor growth by counteracting aberrant angiogenesis and reinforcing antitumor immunity in several experimental settings. Given the multiple therapeutic benefits associated with Gal-1 blockade, several Gal-1 inhibitors, including glycan-based competitors, antagonistic peptides, aptamers and neutralizing monoclonal antibodies, have been designed and evaluated in pre-clinical tumor models. Here we report the biochemical and functional characterization of a newly developed neutralizing anti-human Gal-1 monoclonal antibody (Gal-1-mAb3), which specifically recognizes a unique epitope in Gal-1 protein and exerts both angioregulatory and immunomodulatory activities. Blockade of Gal-1 function using Gal-1-mAb3, might be relevant not only in cancer but also in other pathologic conditions characterized by aberrant angiogenesis and uncontrolled immunosuppression.

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Fig. 1
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Data availability

All data are available in the text and supplementary material.

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Acknowledgements

We thank R.M. Morales and G. Suárez for support in animal care and M. Fernández and E. Malchiodi (IDEHU; CONICET) for support in SPR assays.

Funding

This work was supported by Grants from Agencia Nacional de Promoción Científica y Tecnológica (PICT 2017-0494 to G.A.R. and PICT 2016-0205 to D.O.C.), CONICET (Fondo de Promoción Tecnológica R3449 to G.A.R.) as well as Bunge & Born and Sales Foundations (to G.A.R.)

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Author notes

  1. Juan M. Pérez Sáez, Pablo F. Hockl, Alejando J. Cagnoni contributed equally to this work.

Authors and Affiliations

  1. Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN, Buenos Aires, Argentina

    Juan M. Pérez Sáez, Pablo F. Hockl, Santiago P. Méndez Huergo, Sabrina G. Gatto, Juan P. Cerliani, Diego O. Croci & Gabriel A. Rabinovich

  2. Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), C1428ADN, Buenos Aires, Argentina

    Alejando J. Cagnoni

  3. Facultad de Ciencias Exactas y Naturales, Instituto de Histología y Embriología de Mendoza “Dr. Mario H. Burgos”, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Cuyo, M5500, Mendoza, Argentina

    Pablo A. García & Diego O. Croci

  4. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina

    Gabriel A. Rabinovich

Authors
  1. Juan M. Pérez Sáez
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  2. Pablo F. Hockl
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  3. Alejando J. Cagnoni
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  4. Santiago P. Méndez Huergo
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  5. Pablo A. García
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  6. Sabrina G. Gatto
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  7. Juan P. Cerliani
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  8. Diego O. Croci
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  9. Gabriel A. Rabinovich
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Corresponding authors

Correspondence to Juan M. Pérez Sáez or Gabriel A. Rabinovich.

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All experimental procedures were approved by the Institutional Animal Care and Use Committee at the Institute of Biology and Experimental Medicine (IBYME, CONICET).

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Pérez Sáez, J.M., Hockl, P.F., Cagnoni, A.J. et al. Characterization of a neutralizing anti-human galectin-1 monoclonal antibody with angioregulatory and immunomodulatory activities. Angiogenesis 24, 1–5 (2021). https://doi.org/10.1007/s10456-020-09749-3

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  • DOI: https://doi.org/10.1007/s10456-020-09749-3

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