National Cancer Institute, National Institutes of Health, Center for Cancer Research, Pediatric Oncology Branch, 10 Center Drive, MSC 1104, Bethesda, MD 20892, USA.
Expert Opin Biol Ther. 2010 Feb;10(2):163-78. doi: 10.1517/14712590903431022.
Although most children with cancer are cured, there remain significant limitations of standard treatment, most notably chemotherapy resistance and non-specific toxicities. Novel immune-based therapies that target pediatric malignancies offer attractive adjuncts and/or alternatives to commonly employed cytotoxic regimens of chemotherapy or radiotherapy. Elucidation of the principles of tumor biology and the development of novel laboratory technologies over the last decade have led to substantial progress in bringing immunotherapies to the bedside.
Current immunotherapeutic clinical trials in pediatric oncology and the science behind their development are reviewed.
Most of the immune-based therapies studied to date have been well tolerated, and some have shown promise in the setting of refractory or high-risk malignancies, demonstrating that immunotherapy has the potential to overcome resistance to conventional chemotherapy.
Some immune-based therapies, such as ch14.18 and MTP-PE, have already been proven effective in phase III randomized trials. Further studies are needed to optimize and integrate other therapies into standard regimens, and to test them in randomized trials for patients with childhood cancer.
尽管大多数患有癌症的儿童都能被治愈,但标准治疗仍存在明显的局限性,最明显的是化疗耐药和非特异性毒性。针对儿科恶性肿瘤的新型免疫疗法为常用的化疗或放疗细胞毒性方案提供了有吸引力的辅助治疗和/或替代方案。过去十年中,肿瘤生物学原理的阐明和新实验室技术的发展,使得免疫疗法在临床上取得了实质性进展。
综述了儿科肿瘤学中当前的免疫治疗临床试验及其开发背后的科学。
迄今为止,大多数已研究的基于免疫的疗法耐受性良好,并且一些在难治性或高危恶性肿瘤的情况下显示出前景,表明免疫疗法有可能克服对常规化疗的耐药性。
一些基于免疫的疗法,如 ch14.18 和 MTP-PE,已经在 III 期随机试验中被证明是有效的。需要进一步的研究来优化和整合其他疗法到标准方案中,并在随机试验中测试它们对儿童癌症患者的疗效。