Carbonic Anhydrase IX: A Renewed Target for Cancer Immunotherapy

Cancers

Najla Santos Pacheco de Campos¹  Bruna Santos Souza¹  Gabriela Lagreca¹  Eloah Rabello Suarez¹  Giselle Correia Próspero da Silva¹  Victoria Alves Porto¹  Bassam Janji²  Ghanbar Mahmoodi Chalbatani² 

[1] Center for Natural and Human Sciences, Federal University of ABC, Santo André 09210-580, SP, Brazil;Tumor Immunotherapy and Microenvironment (TIME) Group, Department of Cancer Research, Luxembourg Institute of Health, 1445 Luxembourg, Luxembourg;

关键词: chimeric antigen receptor;    antitumor monoclonal antibodies;    clear cell renal cell cancer;    hypoxic tumors;    immunotherapies;    immune checkpoint inhibitors;   

DOI  :  10.3390/cancers14061392

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown