Rosenblatt Jacalyn, Kufe Donald, Avigan David
Hematologic Malignancy Bone Marrow Transplant Program, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, KS 121, Boston, MA 02215, USA.
Expert Opin Biol Ther. 2005 May;5(5):703-15. doi: 10.1517/14712598.5.5.703.
The use of tumour vaccines is being explored as a means of generating effective antitumour immune responses in patients with cancer. Dendritic cells (DCs) are the most potent antigen-presenting cells that are essential for initiating primary immune responses. As such, DCs are being studied as a platform for the design of cancer vaccines. DCs loaded with tumour antigens or whole tumour cell derivatives stimulate tumour-specific immunity. A promising vaccine strategy involves the fusion of DCs with whole tumour cells. DC/tumour fusions express a broad array of tumour antigens, including those yet to be identified, in the context of DC-mediated costimulation. Animal models have demonstrated that vaccination with fusion cells is protective against tumour challenge and results in the regression of established metastatic disease. In vitro human studies have demonstrated that DC/tumour fusions potently stimulate antitumour immunity and lysis of autologous tumour cells. Vaccination of cancer patients with DC/tumour fusions is being studied in Phase I/II clinical trials. Preliminary results demonstrate that generation of a vaccine is feasible and that vaccination is associated with minimal toxicity. Immunological and clinical responses have been found in a subset of patients.
肿瘤疫苗的应用正在被探索,作为在癌症患者中产生有效的抗肿瘤免疫反应的一种手段。树突状细胞(DCs)是启动初次免疫反应所必需的最有效的抗原呈递细胞。因此,DCs正被作为癌症疫苗设计的一个平台进行研究。负载肿瘤抗原或全肿瘤细胞衍生物的DCs可刺激肿瘤特异性免疫。一种有前景的疫苗策略涉及DCs与全肿瘤细胞的融合。DC/肿瘤融合细胞在DC介导的共刺激作用下表达多种肿瘤抗原,包括那些尚未被鉴定的抗原。动物模型已证明,用融合细胞进行疫苗接种可预防肿瘤攻击,并导致已建立的转移性疾病消退。体外人体研究已证明,DC/肿瘤融合细胞能有效刺激抗肿瘤免疫并裂解自体肿瘤细胞。用DC/肿瘤融合细胞对癌症患者进行疫苗接种正在进行I/II期临床试验。初步结果表明,疫苗的产生是可行的,且疫苗接种的毒性极小。在一部分患者中发现了免疫和临床反应。