Immunotherapy of hematologic malignancy.
Immunotherapy of hematologic malignancy.
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DOI：
10.1182/asheducation-2003.1.331
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
H. Heslop;F. Stevenson;J. Molldrem
中科院分区：
文献类型：
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作者：
H. Heslop;F. Stevenson;J. Molldrem
在过去的几年中，对抗原提呈细胞和效应细胞之间相互作用的分子基础的理解的提高以及信息学的进步都导致了许多候选抗原的鉴定，这些抗原是免疫治疗的靶点。然而，尽管免疫疗法已经成功根除了同种异体移植后复发的恶性血液病以及病毒诱导的肿瘤，但将免疫疗法扩展到更广泛的恶性血液病方面仍存在局限性。本文综述了三种免疫治疗策略及其改进方法。在第一节中，Stevenson博士回顾了基因疫苗单独通过裸DNA或病毒载体传递的临床经验，这在淋巴瘤和骨髓瘤患者的临床试验中显示出希望。她描述了操纵基因结构以增强免疫原性和添加额外元素以产生更持久的免疫反应的努力。在第二节中，Molldrem博士描述了肽疫苗的临床经验，特别关注髓系组织限制性蛋白作为CML和AML的GVL靶抗原。蛋白酶3和其他azurophil颗粒蛋白可能是自体和异体t细胞反应的特别好的靶标。肽疫苗的效力可能通过基因修饰肽来增强t细胞受体的亲和力而潜在地增加。最后，在第三部分，Heslop博士回顾了T细胞过继免疫治疗的临床经验。转移T细胞在治疗移植后复发的恶性肿瘤和eb病毒相关肿瘤方面具有临床益处。然而，由于过继转移细胞的持久性或扩散性不足以及肿瘤逃避机制的存在，T细胞在治疗其他血液系统恶性肿瘤方面不太成功。提高对抗原提呈细胞与T细胞相互作用的理解，可以优化制造效应T细胞的努力，而体内淋巴细胞稳态的操纵和基因治疗方法的发展可能会增强过继转移T细胞的持久性和功能。
Over the past few years, improved understanding of the molecular basis of interactions between antigen presenting cells and effector cells and advances in informatics have both led to the identification of many candidate antigens that are targets for immunotherapy. However, while immunotherapy has successfully eradicated relapsed hematologic malignancy after allogeneic transplant as well as virally induced tumors, limitations have been identified in extending immunotherapy to a wider range of hematologic malignancies. This review provides an overview of three immunotherapy strategies and how they may be improved. In Section I, Dr. Stevenson reviews the clinical experience with genetic vaccines delivered through naked DNA alone or viral vectors, which are showing promise in clinical trials in lymphoma and myeloma patients. She describes efforts to manipulate constructs genetically to enhance immunogenicity and to add additional elements to generate a more sustained immune response. In Section II, Dr. Molldrem describes clinical experience with peptide vaccines, with a particular focus on myeloid tissue-restricted proteins as GVL target antigens in CML and AML. Proteinase 3 and other azurophil granule proteins may be particularly good targets for both autologous and allogeneic T-cell responses. The potency of peptide vaccines may potentially be increased by genetically modifying peptides to enhance T-cell receptor affinity. Finally, in Section III, Dr. Heslop reviews clinical experience with adoptive immunotherapy with T cells. Transferred T cells have clinical benefit in treating relapsed malignancy post transplant, and Epstein-Barr virus associated tumors. However, T cells have been less successful in treating other hematologic malignancies due to inadequate persistence or expansion of adoptively transferred cells and the presence of tumor evasion mechanisms. An improved understanding of the interactions of antigen presenting cells with T cells should optimize efforts to manufacture effector T cells, while manipulation of lymphocyte homeostasis in vivo and development of gene therapy approaches may enhance the persistence and function of adoptively transferred T cells.