Cytokines as Adjuvants for Vaccine and Cellular Therapies for Cancer.
Cytokines as Adjuvants for Vaccine and Cellular Therapies for Cancer.
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DOI：
10.3844/ajisp.2009.65.83
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发表时间：
2009-01-01
期刊：
影响因子：
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通讯作者：
Mackall CL
中科院分区：
文献类型：
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作者：
Capitini CM;Fry TJ;Mackall CL
一种能够帮助治疗对传统细胞毒疗法具有耐药性的肿瘤的有效疫苗的开发仍然难以捉摸。虽然部分问题可能是因为试验的重点是巨大的残留疾病患者，但人们仍然希望最大限度地提高对疫苗的反应。细胞因子的伽马(C)家族提供了一个独特的机会来支持疫苗反应T细胞的扩增和效应器潜力，以及刺激其他效应器，如自然杀伤(NK)细胞被激活。将疫苗与细胞因子结合似乎合乎逻辑，但可能会带来不想要的毒性，就像白细胞介素2(IL-2)所观察到的那样。此外，不需要的细胞亚群的非特异性激活或扩张，如调节性T细胞，可能会导致全球免疫抑制并限制疫苗反应。IL-7和IL-21的开发为临床提供了增强抗肿瘤反应的前景，但全身毒性要小得多，而且不会增加调节性T细胞。临床前研究表明，IL-15还可以改善T细胞，特别是NK细胞的反应。未来的工作应该扩大IL-7、IL-21和IL-15疫苗在高危患者中的使用，并考虑在残留疾病最小的状态下进行治疗，以最大限度地提高效益。识别能够通过伽马(C)细胞因子发出信号的肿瘤也是至关重要的，这样才能避免复发的诱导。
The development of a potent vaccine that can help treat tumors resistant to conventional cytotoxic therapies remains elusive. While part of the problem may be that trials have focused on patients with bulky residual disease, the desire to maximize responses to the vaccine remains. The gamma(c) family of cytokines offer a unique opportunity to support the expansion and effector potential of vaccine-responding T-cells, as well as stimulate other effectors, such as natural killer (NK) cells, to become activated. Combining vaccines with cytokines seems logical but can bring unwanted toxicity, as has been observed with interleukin (IL)-2. In addition, the nonspecific activation or expansion of unwanted cell subsets, such as regulatory T-cells, can contribute to global immunosuppression and limit vaccine responses. The development of IL-7 and IL-21 for the clinic offers the promise of enhancing anti-tumor responses but with far less systemic toxicity and no expansion of regulatory T cells. Preclinical studies demonstrate that IL-15 could also improve T-cell, and especially NK-cell, responses as well. Future work should expand the use of vaccines with IL-7, IL-21 and hopefully IL-15 in high-risk patients, and consider treatment while in a state of minimal residual disease to maximize benefit. Identifying tumors that can signal through gamma(c) cytokines will also be essential so that induction of relapse will be avoided.