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e-Posters

55P - Clinical Landscape of LAG-3-Targeted Therapy

Date

06 Oct 2021

Session

e-Posters

Presenters

Luisa Chocarro

Citation

Annals of Oncology (2021) 32 (suppl_6): S1345-S1371. 10.1016/annonc/annonc740

Authors

L. Chocarro1, E. Blanco2, H. Arasanz3, A. Bocanegra2, L. Fernández-Rubio2, M. Echaide2, M. Garnica2, P. Ramos2, G. Fernández-Hinojal3, R. Vera3, G. Kochan2, D. Escors2

Author affiliations

  • 1 Navarrabiomed-Public University of Navarre, IdISNA, Pamplona/ES
  • 2 Navarrabiomed-Public University of Navarre, IdISNA, 31008 - Pamplona/ES
  • 3 Complejo Hospitalario de Navarra CHN-IdISNA, 31008 - Pamplona/ES
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Abstract 55P

Background

Lymphocyte-activating gene-3 (LAG-3) is a cell surface inhibitory receptor with multiple biological activities over T cell activation and effector functions. LAG-3 is the third inhibitory receptor to be exploited in human anti-cancer immunotherapies. LAG-3 is considered a next-generation target in cancer immunotherapy, right next to PD-1 and CTLA-4.

Methods

Several LAG-3 blockade immunotherapeutic models are being pursued at various stages of clinical and pre-clinical development. An extensive bibliographic research was performed using Pubmed and Clinicaltrials.gov databases to identify preclinical and clinical trials conducted up to date involving LAG-3 as a target. Here we summarize the current understanding of LAG-3 clinical applications.

Results

LAG-3 was first used in clinical trials in 2006 as a LAG-3-Ig soluble fusion protein, but as an immune stimulator. Nowadays, several LAG-3-antagonistic immunotherapeutic models are being evaluated at various stages of clinical and pre-clinical development. In addition, combinations blocking LAG-3 together with other immune checkpoints are also being characterized. A new generation of bispecific PD-1/LAG-3 blocking agents have shown strong capacities to specifically target PD-1+ LAG-3+ highly dysfunctional T cells and enhance their proliferation and effector activities.

Conclusions

LAG-3 is a key regulator of immune homeostasis and a highly important next-generation immune checkpoint. Anti-LAG-3 antibodies and combinations are being evaluated at preclinical and clinical levels. Indeed, the co-blockade of LAG-3 with PD-1 is showing encouraging results. A deeper understanding of the basic mechanisms underlying LAG-3 intracellular signaling will provide insight for further development of novel strategies for cancer targeted treatment.

Legal entity responsible for the study

Navarrabiomed.

Funding

Association Against Cancer (AECC, PROYE16001ESCO); Instituto de Salud Carlos III (ISCIII)-FEDER project grants (FIS PI17/02119, FIS PI20/00010, COV20/00000, and TRANSPOCART ICI19/00069); a Biomedicine Project grant from the Department of Health of the Government of Navarre (BMED 050-2019); Strategic projects from the Department of Industry, Government of Navarre (AGATA, Ref 0011-1411-2020-000013; LINTERNA, Ref. 0011-1411-2020-000033; DESCARTHES, 0011-1411-2019-000058); European Project Horizon 2020 Improved Vaccination for Older Adults (ISOLDA; ID: 848166); Crescendo Biologics Ltd.

Disclosure

All authors have declared no conflicts of interest.

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