TY - JOUR
T1 - Carbonic Anhydrase IX
T2 - A Renewed Target for Cancer Immunotherapy
AU - de Campos, Najla Santos Pacheco
AU - Souza, Bruna Santos
AU - da Silva, Giselle Correia Próspero
AU - Porto, Victoria Alves
AU - Chalbatani, Ghanbar Mahmoodi
AU - Lagreca, Gabriela
AU - Janji, Bassam
AU - Suarez, Eloah Rabello
N1 - Funding Information:
Funding: This work was supported by the Luxembourg National Research Fund (BRIDGES2020/BM/ 15412275/SMART COMBO), Fondation Recherche Cancer et Sang, Luxembourg (INCOM BIOM) and São Paulo Research Foundation under Grant #2018/17656-0.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3/9
Y1 - 2022/3/9
N2 - 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.
AB - 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.
KW - Antitumor monoclonal antibodies
KW - Carbonic anhydrase
KW - Chimeric antigen receptor
KW - Clear cell renal cell cancer
KW - Hypoxic tumors
KW - Immune checkpoint inhibitors
KW - Immunotherapies
UR - http://www.scopus.com/inward/record.url?scp=85125888633&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/35326544
U2 - 10.3390/cancers14061392
DO - 10.3390/cancers14061392
M3 - Review article
C2 - 35326544
AN - SCOPUS:85125888633
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 6
M1 - 1392
ER -