Gilboa E, Nair S K, Lyerly H K
Center for Genetic and Cellular Therapies, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Cancer Immunol Immunother. 1998 Apr;46(2):82-7. doi: 10.1007/s002620050465.
Animal studies have shown that vaccination with genetically modified tumor cells or with dendritic cells (DC) pulsed with tumor antigens are potent strategies to elicit protective immunity in tumor-bearing animals, more potent than "conventional" strategies that have been tested in clinical settings with limited success. While both vaccination strategies are forms of cell therapy requiring complex and costly ex vivo manipulations of the patient's cells, current protocols using dendritic cells are considerably simpler and would be more widely available. Vaccination with defined tumor antigens presented by DC has obvious appeal. However, in view of the expected emergence of antigen-loss variants as well as natural immunovariation, effective vaccine formulations must contain mixtures of commonly, if not universally, expressed tumor antigens. When, or even if, such common tumor antigens will be identified cannot be, predicted, however. Thus, for the foreseeable future, vaccination with total-tumor-derived material as source of tumor antigens may be preferable to using defined tumor antigens. Vaccination with undefined tumor-derived antigens will be limited, however, by the availability of sufficient tumor tissue for antigen preparation. Because the mRNA content of single cells can be amplified, tumor mRNA, or corresponding cDNA libraries, offer an unlimited source of tumor antigens. DC transfected with tumor RNA were shown to engender potent antitumor immunity in animal studies. Thus, immunotherapy using autologous DC loaded with unfractionated tumor-derived antigens in the form of RNA emerges as a potentially powerful and broadly useful vaccination strategy for cancer patients.
动物研究表明，用基因改造的肿瘤细胞或用负载肿瘤抗原的树突状细胞（DC）进行疫苗接种是在荷瘤动物中引发保护性免疫的有效策略，比在临床环境中测试但效果有限的“传统”策略更有效。虽然这两种疫苗接种策略都是细胞疗法的形式，需要对患者细胞进行复杂且昂贵的体外操作，但目前使用树突状细胞的方案要简单得多，并且更容易获得。用DC呈递的特定肿瘤抗原进行疫苗接种具有明显的吸引力。然而，鉴于预计会出现抗原丢失变体以及自然免疫变异，有效的疫苗制剂必须包含通常（即使不是普遍）表达的肿瘤抗原的混合物。然而，何时甚至是否能鉴定出这种常见的肿瘤抗原是无法预测的。因此，在可预见的未来，用全肿瘤来源的材料作为肿瘤抗原的来源进行疫苗接种可能比使用特定的肿瘤抗原更可取。然而，用未定义的肿瘤衍生抗原进行疫苗接种将受到制备抗原所需足够肿瘤组织可用性的限制。由于单细胞的mRNA含量可以扩增，肿瘤mRNA或相应的cDNA文库提供了无限的肿瘤抗原来源。在动物研究中，用肿瘤RNA转染的DC显示出能产生强大的抗肿瘤免疫力。因此，使用负载有未分级肿瘤衍生抗原RNA形式的自体DC进行免疫治疗，成为一种对癌症患者潜在强大且广泛有用的疫苗接种策略。
