Carbonic Anhydrase IX: A Renewed Target for Cancer Immunotherapy

Najla Santos Pacheco de Campos, Bruna Santos Souza, Giselle Correia Próspero da Silva, Victoria Alves Porto, Ghanbar Mahmoodi Chalbatani, Gabriela Lagreca, Bassam Janji*, Eloah Rabello Suarez

*Corresponding author for this work

Research output: Contribution to journalReview articleResearchpeer-review

1 Citation (Scopus)

Abstract

The carbonic anhydrase isoform IX (CAIX) enzyme is constitutively overexpressed in the vast majority of clear cell renal cell carcinoma (ccRCC) and can also be induced in hypoxic microenvironments, a major hallmark of most solid tumors. CAIX expression is restricted to a few sites in healthy tissues, positioning this molecule as a strategic target for cancer immunotherapy. In this review, we summarized preclinical and clinical data of immunotherapeutic strategies based on monoclonal antibodies (mAbs), fusion proteins, chimeric antigen receptor (CAR) T, and NK cells targeting CAIX against different types of solid malignant tumors, alone or in combination with radionuclides, cytokines, cytotoxic agents, tyrosine kinase inhibitors, or immune checkpoint blockade. Most clinical studies targeting CAIX for immunotherapy were performed using G250 mAb-based antibodies or CAR T cells, developed primarily for bioimaging purposes, with a limited clinical response for ccRCC. Other anti-CAIX mAbs, CAR T, and NK cells developed with therapeutic intent presented herein offered outstanding preclinical results, justifying further exploration in the clinical setting.

Original languageEnglish
Article number1392
JournalCancers
Volume14
Issue number6
DOIs
Publication statusPublished - 9 Mar 2022

Keywords

  • Antitumor monoclonal antibodies
  • Carbonic anhydrase
  • Chimeric antigen receptor
  • Clear cell renal cell cancer
  • Hypoxic tumors
  • Immune checkpoint inhibitors
  • Immunotherapies

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