Chandran Mayuri, Candolfi Marianela, Shah Diana, Mineharu Yohei, Yadav Viveka Nand, Koschmann Carl, Asad Antonela S, Lowenstein Pedro R, Castro Maria G
a Department of Neurosurgery , The University of Michigan School of Medicine, MSRB II , Ann Arbor , MI , USA.
b Department of Cell and Developmental Biology , The University of Michigan School of Medicine , Ann Arbor , MI , USA.
Expert Opin Biol Ther. 2017 May;17(5):543-554. doi: 10.1080/14712598.2017.1305353. Epub 2017 Mar 20.
Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific features may substantially improve upon existing treatments. Areas covered: Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies. In this review, the authors discuss emerging combinations of immunotherapies and compare efficacy of single vs. combined therapies tested in preclinical brain tumor models. Expert opinion: Malignant gliomas are characterized by a number of factors which may limit the success of single immunotherapies including inter-tumor and intra-tumor heterogeneity, intrinsic resistance to traditional therapies, immunosuppression, and immune selection for tumor cells with low antigenicity. Combination of therapies which target multiple aspects of tumor physiology are likely to be more effective than single therapies. While a limited number of combination immunotherapies are described which are currently being tested in preclinical and clinical studies, the field is expanding at an astounding rate, and endless combinations remain open for exploration.
恶性胶质瘤是具有高度侵袭性的肿瘤,尽管采用了包括手术切除、放疗和替莫唑胺(TMZ)化疗在内的标准治疗方案,其生存率仍令人沮丧。针对独特肿瘤特异性特征的精准免疫疗法或免疫疗法组合可能会显著改善现有治疗方法。涵盖领域:单一免疫疗法的临床试验已显示出对高级别胶质瘤患者具有治疗潜力,并且新出现的临床前研究表明,免疫疗法组合可能比单一疗法更有效。在本综述中,作者讨论了免疫疗法的新兴组合,并比较了在临床前脑肿瘤模型中测试的单一疗法与联合疗法的疗效。专家观点:恶性胶质瘤具有多种因素,可能会限制单一免疫疗法的成功,包括肿瘤间和肿瘤内的异质性、对传统疗法的固有抗性、免疫抑制以及对低抗原性肿瘤细胞的免疫选择。针对肿瘤生理学多个方面的联合疗法可能比单一疗法更有效。虽然目前在临床前和临床研究中测试的联合免疫疗法数量有限,但该领域正在以惊人的速度扩展,并且仍有无数组合有待探索。