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用于儿童恶性肿瘤的治疗性癌症疫苗:进展、挑战与新兴技术

Therapeutic cancer vaccines for pediatric malignancies: advances, challenges, and emerging technologies.

作者信息

Olsen Hannah E, Lynn Geoffrey M, Valdes Pablo A, Cerecedo Lopez Christian D, Ishizuka Andrew S, Arnaout Omar, Bi W Linda, Peruzzi Pier Paolo, Chiocca E Antonio, Friedman Gregory K, Bernstock Joshua D

机构信息

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Avidea Technologies, Inc., Baltimore, Maryland, USA.

出版信息

Neurooncol Adv. 2021 Feb 11;3(1):vdab027. doi: 10.1093/noajnl/vdab027. eCollection 2021 Jan-Dec.

Abstract

Though outcomes for pediatric cancer patients have significantly improved over the past several decades, too many children still experience poor outcomes and survivors suffer lifelong, debilitating late effects after conventional chemotherapy, radiation, and surgical treatment. Consequently, there has been a renewed focus on developing novel targeted therapies to improve survival outcomes. Cancer vaccines are a promising type of immunotherapy that leverage the immune system to mediate targeted, tumor-specific killing through recognition of tumor antigens, thereby minimizing off-target toxicity. As such, cancer vaccines are orthogonal to conventional cancer treatments and can therefore be used alone or in combination with other therapeutic modalities to maximize efficacy. To date, cancer vaccination has remained largely understudied in the pediatric population. In this review, we discuss the different types of tumor antigens and vaccine technologies (dendritic cells, peptides, nucleic acids, and viral vectors) evaluated in clinical trials, with a focus on those used in children. We conclude with perspectives on how advances in combination therapies, tumor antigen (eg, neoantigen) selection, and vaccine platform optimization can be translated into clinical practice to improve outcomes for children with cancer.

摘要

尽管在过去几十年里,儿科癌症患者的治疗结果有了显著改善,但仍有太多儿童预后不良,幸存者在接受传统化疗、放疗和手术治疗后,会遭受终身的、使人衰弱的后期影响。因此,人们重新将重点放在开发新型靶向治疗方法上,以改善生存结果。癌症疫苗是一种很有前景的免疫疗法,它利用免疫系统通过识别肿瘤抗原来介导靶向的、肿瘤特异性杀伤,从而将脱靶毒性降至最低。因此,癌症疫苗与传统癌症治疗方法不同,因此可以单独使用或与其他治疗方式联合使用,以最大限度地提高疗效。迄今为止,癌症疫苗在儿科人群中的研究仍非常有限。在这篇综述中,我们讨论了在临床试验中评估的不同类型的肿瘤抗原和疫苗技术(树突状细胞、肽、核酸和病毒载体),重点关注在儿童中使用的那些。我们最后展望了联合疗法、肿瘤抗原(如新生抗原)选择和疫苗平台优化方面的进展如何转化为临床实践,以改善癌症儿童的治疗结果。

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