TIM-3: a tumor-associated antigen beyond checkpoint inhibition?

Stefan Barth; Krupa Naran

doi:10.1093/immadv/ltac021

TIM-3: a tumor-associated antigen beyond checkpoint inhibition?

Immunother Adv. 2022 Oct 21;2(1):ltac021. doi: 10.1093/immadv/ltac021. eCollection 2022.

Authors

Stefan Barth^{1

2}, Krupa Naran¹

Affiliations

¹ Medical Biotechnology and Immunotherapy Research Unit, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
² South African Research Chair in Cancer Biotechnology, Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Abstract

Immune checkpoint inhibitors are one of the most remarkable immunomodulatory therapies of current times. Sabatolimab is a high-affinity, humanized anti-TIM-3 monoclonal antibody currently in development for patients with myeloproliferative disorders, including acute myeloid leukemia and myelodysplastic syndromes. By targeting TIM-3, a receptor expressed on various immune effector cells as well as myeloid cells, multiple mechanisms of action that are distinct from canonical immune checkpoint inhibitors are in play - (i) blockade of TIM-3 and its ligands PtdSer/galectin-9, (ii) modulation of leukemic cell self-renewal as well as (iii) antibody-dependent phagocytosis of TIM-3-expressing leukemic cells. Novel immunotherapies such as sabatolimab which enhance the antitumor immune response on converging fronts represent the promise of a continuously replenished armoury for the treatment of cancer.

Keywords: TIM-3; antigen; checkpoint; inhibition; tumor-associated.