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

Lucia Lisi, Pedro Miguel Lacal, Maria Martire, Pierluigi Navarra*, Grazia Graziani, Giovanni Graziani

*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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.
Lingua originaleEnglish
pagine (da-a)105997-N/A
RivistaPharmacological Research
Volume175
DOI
Stato di pubblicazionePubblicato - 2022

Keywords

  • Animals
  • Antibodies, Bispecific
  • Antineoplastic Agents, Immunological
  • CTLA-4
  • CTLA-4 Antigen
  • Humans
  • Immune checkpoint inhibitors
  • Immunotherapy
  • Ipilimumab
  • Melanoma
  • Monoclonal antibodies
  • Neoplasms
  • PD-1
  • PD-L1
  • Tumor Microenvironment

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