Data di Pubblicazione:
2021
Citazione:
Depleting tumor cells expressing immune checkpoint ligands—a new approach to combat cancer / F. Marcucci, C. Rumio. - In: CELLS. - ISSN 2073-4409. - 10:4(2021 Apr 12), pp. 872.1-872.23. [10.3390/cells10040872]
Abstract:
Antibodies against inhibitory immune checkpoint molecules (ICPMs), referred to as immune checkpoint inhibitors (ICIs), have gained a prominent place in cancer therapy. Several ICIs in clinical use have been engineered to be devoid of effector functions because of the fear that ICIs with preserved effector functions could deplete immune cells, thereby curtailing antitumor immune responses. ICPM ligands (ICPMLs), however, are often overexpressed on a sizeable fraction of tumor cells of many tumor types and these tumor cells display an aggressive phenotype with changes typical of tumor cells undergoing an epithelial-mesenchymal transition. Moreover, immune cells expressing ICPMLs are often endowed with immunosuppressive or immune-deviated functionalities. Taken together, these observations suggest that compounds with the potential of depleting cells expressing ICPMLs may become useful tools for tumor therapy. In this article, we summarize the current state of the art of these compounds, including avelumab, which is the only ICI targeting an ICPML with preserved effector functions that has gained approval so far. We also discuss approaches allowing to obtain compounds with enhanced tumor cell-depleting potential compared to native antibodies. Eventually, we propose treatment protocols that may be applied in order to optimize the therapeutic efficacy of compounds that deplete cells expressing ICPMLs.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
ADC; bispecific; CAR T cells; combination therapy; effector functions; epithelial-mesenchymal transition; immune checkpoint; oncolytic virus; overexpression; antibodies, neoplasm; humans; immune checkpoint inhibitors; immune checkpoint proteins; ligands; neoplasms; treatment outcome
Elenco autori:
F. Marcucci, C. Rumio
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