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Clinical experience with CTLA-4 blockade for cancer immunotherapy: From the monospecific monoclonal antibody ipilimumab to probodies and bispecific molecules targeting the tumor microenvironment.

Clinical experience with CTLA-4 blockade for cancer immunotherapy: From the monospecific monoclonal antibody ipilimumab to probodies and bispecific molecules targeting the tumor microenvironment.

Authors :
Lisi L
Lacal PM
Martire M
Navarra P
Graziani G
Source :
Pharmacological research [Pharmacol Res] 2022 Jan; Vol. 175, pp. 105997. Date of Electronic Publication: 2021 Nov 24.
Publication Year :
2022

Abstract

The immune checkpoint cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is an inhibitory regulator of T-cell mediated responses that has been investigated as target of monoclonal antibodies (mAbs) for cancer immunotherapy. The anti-CTLA-4 mAb ipilimumab represents the first immune checkpoint inhibitor that significantly improved overall survival in patients with unresectable/metastatic melanoma. The subsequent approved indications (often in the first-line setting) for melanoma and other advanced/metastatic solid tumors always require ipilimumab combination with nivolumab, an anti-programmed cell death protein 1 (PD-1) mAb. However, the improved clinical efficacy of the mAb combination is associated with increased immune-related adverse events, which might require treatment discontinuation even in responding patients. This drawback is expected to be overcome by the recent development of anti-CTLA-4 probodies proteolitycally activated in the tumor microenvironment and bispecific molecules targeting both CTLA-4 and PD-1, whose co-expression is characteristic of tumor-infiltrating T cells. These molecules would preferentially stimulate immune responses against the tumor, reducing toxicity toward normal tissues.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1096-1186
Volume :
175
Database :
MEDLINE
Journal :
Pharmacological research
Publication Type :
Academic Journal
Accession number :
34826600
Full Text :
https://doi.org/10.1016/j.phrs.2021.105997