Hadzantonis M, O'Neill H
Division of Biochemistry & Molecular Biology School of Life Sciences, Australian National University, Canberra ACT, Australia.
Cancer Biother Radiopharm. 1999 Feb;14(1):11-22. doi: 10.1089/cbr.1999.14.11.
Melanoma is a particularly aggressive malignant tumour of the skin that is influenced by genetic, environmental and physiological elements. Since current therapy for melanoma is limited and associated with high toxicity and side effects, development of alternative approaches is imperative. The importance of dendritic cells (DCs) in immunity against tumours is now well established. DC immunotherapy for melanoma is possible but must be considered in terms of effectiveness and clinical viability. The source of DCs to be used in adoptive therapy as well as the nature and method of delivery of the priming antigen are important factors. The most suitable DC appears to be cells derived by culture from hemopoietic progenitor cells (HPC) in bone marrow or DC progenitors in peripheral blood. Generation of an effective anti-tumour immune response will be dependent upon the presentation of multiple melanoma-specific antigens by both major histocompatibility complex (MHC) class I and class II molecules and stimulation of both tumour-specific cytotoxic T lymphocytes (Tc) and T helper type 1 (Thl) cells. Different techniques for delivery of the priming antigen offer different advantages. DCs can be pulsed with peptide, protein or tumour cell lysate, transfected with viral vectors or naked nucleic acid and tumour/DC hybridomas can also be generated. Repeated antigen administration into neighbouring lymph nodes appears to be the most effective method for promoting a systemic anti-tumour response. Adjuvant therapies can also enhance immune responses and lead to total tumour clearance. The importance of DC immunotherapy in clinically different stages of disease will also be an important consideration.
黑色素瘤是一种侵袭性很强的皮肤恶性肿瘤，受遗传、环境和生理因素影响。由于目前黑色素瘤的治疗方法有限，且伴有高毒性和副作用，因此必须开发替代方法。树突状细胞（DCs）在抗肿瘤免疫中的重要性现已得到充分证实。DC免疫疗法对黑色素瘤是可行的，但必须从有效性和临床可行性方面加以考虑。用于过继性治疗的DC来源以及致敏抗原的性质和递送方法都是重要因素。最合适的DC似乎是通过培养从骨髓中的造血祖细胞（HPC）或外周血中的DC祖细胞衍生而来的细胞。有效的抗肿瘤免疫反应的产生将取决于主要组织相容性复合体（MHC）I类和II类分子呈递多种黑色素瘤特异性抗原，以及刺激肿瘤特异性细胞毒性T淋巴细胞（Tc）和1型辅助性T细胞（Thl）。不同的致敏抗原递送技术具有不同的优势。DC可以用肽、蛋白质或肿瘤细胞裂解物脉冲处理，用病毒载体或裸核酸转染，也可以产生肿瘤/DC杂交瘤。向邻近淋巴结反复给予抗原似乎是促进全身性抗肿瘤反应的最有效方法。辅助治疗也可以增强免疫反应并导致肿瘤完全清除。DC免疫疗法在临床上不同疾病阶段的重要性也将是一个重要的考虑因素。
