Campos Najla Santos Pacheco de, Souza Bruna Santos, Silva Giselle Correia Próspero da, Porto Victoria Alves, Chalbatani Ghanbar Mahmoodi, Lagreca Gabriela, Janji Bassam, Suarez Eloah Rabello
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.
Cancers (Basel). 2022 Mar 9;14(6):1392. doi: 10.3390/cancers14061392.
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.
碳酸酐酶同工酶IX（CAIX）在绝大多数透明细胞肾细胞癌（ccRCC）中持续过度表达，并且在缺氧微环境中也可被诱导，而缺氧微环境是大多数实体瘤的一个主要特征。CAIX的表达在健康组织中仅限于少数部位，这使得该分子成为癌症免疫治疗的一个战略靶点。在本综述中，我们总结了基于单克隆抗体（mAb）、融合蛋白、嵌合抗原受体（CAR）T细胞和NK细胞靶向CAIX针对不同类型实体恶性肿瘤的免疫治疗策略的临床前和临床数据，这些策略单独使用或与放射性核素、细胞因子、细胞毒性药物、酪氨酸激酶抑制剂或免疫检查点阻断联合使用。大多数针对CAIX进行免疫治疗的临床研究使用的是基于G250 mAb的抗体或CAR T细胞，这些主要是为生物成像目的而开发的，对ccRCC的临床反应有限。本文介绍的其他具有治疗意图而开发的抗CAIX mAb、CAR T细胞和NK细胞展现出了出色的临床前结果，证明在临床环境中进一步探索是合理的。
