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引用次数: 0
摘要
尽管嵌合抗原受体(CAR)T细胞在B细胞恶性肿瘤和多发性骨髓瘤患者中取得了巨大成功,但它们对大多数实体瘤的疗效仍然有限。特别是在儿科人群中,由于伦理原因,很少进行治疗前后的活组织检查,因此,我们对肿瘤微环境中肿瘤细胞排斥效应细胞和吸引免疫抑制细胞的机制的了解仍然非常有限。尽管如此,基于已知的原理,目前的 T 细胞工程已经利用了其中的一些过程,并创造出了更强大的 CAR T 细胞。最近发现的新胎盘抗原和 CAR 设计方面取得的进展扩大了治疗开发候选抗原的潜在库。增强 CAR T 细胞最有希望的方法是新型 CAR 门控策略、在不增加全身毒性的情况下向 TME 运送细胞因子的创新方法,以及劫持肿瘤趋化因子轴以达到迁移目的。有了这些新的修改,CAR T 细胞开发时代的下一步将是对这些前景光明的临床前研究成果进行临床验证。
CAR T-cells for pediatric solid tumors: where to go from here?
Despite the great success that chimeric antigen receptor (CAR) T-cells have had in patients with B-cell malignancies and multiple myeloma, they continue to have limited efficacy against most solid tumors. Especially in the pediatric population, pre- and post-treatment biopsies are rarely performed due to ethical reasons, and thus, our understanding is still very limited regarding the mechanisms in the tumor microenvironment by which tumor cells exclude effectors and attract immune-suppressive cells. Nevertheless, based on the principles that are known, current T-cell engineering has leveraged some of these processes and created more potent CAR T-cells. The recent discovery of new oncofetal antigens and progress made in CAR design have expanded the potential pool of candidate antigens for therapeutic development. The most promising approaches to enhance CAR T-cells are novel CAR gating strategies, creative ways of cytokine delivery to the TME without enhancing systemic toxicity, and hijacking the chemokine axis of tumors for migratory purposes. With these new modifications, the next step in the era of CAR T-cell development will be the clinical validation of these promising preclinical findings.
期刊介绍:
Contemporary biomedical research is on the threshold of an era in which physiological and pathological processes can be analyzed in increasingly precise and mechanistic terms.The transformation of biology from a largely descriptive, phenomenological discipline to one in which the regulatory principles can be understood and manipulated with predictability brings a new dimension to the study of cancer and the search for effective therapeutic modalities for this disease. Cancer and Metastasis Reviews provides a forum for critical review and discussion of these challenging developments.
A major function of the journal is to review some of the more important and interesting recent developments in the biology and treatment of malignant disease, as well as to highlight new and promising directions, be they technological or conceptual. Contributors are encouraged to review their personal work and be speculative.