Dao Tao, Scheinberg David A
Molecular Pharmacology & Chemistry Program, Leukemia Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Best Pract Res Clin Haematol. 2008 Sep;21(3):391-404. doi: 10.1016/j.beha.2008.05.001.
The development of cancer vaccines directed against myeloid leukaemias has been a research area of intense interest in the past decade. Both human studies in vitro and mouse models in vivo have demonstrated that leukaemia-associated antigens (LAAs), such as the fusion protein BCR-ABL, Wilms' tumour protein and proteinase 3, may serve as effective targets for cellular immunotherapy. Peptide-based vaccines are able to induce cytotoxic T-lymphocyte responses that kill leukaemia cells. Based on these results, pilot clinical trials have been initiated in chronic and acute myeloid leukaemia and other haematological malignancies, which include vaccination of patients with synthetic peptides derived from these LAAs. Results from these trials show that peptide vaccines are able to induce immune responses that are sometimes associated with clinical benefit. These early clinical results are promising and provide valuable information for future improvement of the vaccines. This chapter will focus mainly on discussing the preclinical studies of peptide vaccines in human systems, the results from clinical trials and the future prospects for vaccine therapy for myeloid leukaemia.
在过去十年中,针对髓系白血病的癌症疫苗研发一直是一个备受关注的研究领域。体外人体研究和体内小鼠模型均已表明,白血病相关抗原(LAA),如融合蛋白BCR-ABL、肾母细胞瘤蛋白和蛋白酶3,可能成为细胞免疫治疗的有效靶点。基于肽的疫苗能够诱导细胞毒性T淋巴细胞反应,从而杀死白血病细胞。基于这些结果,已在慢性和急性髓系白血病以及其他血液系统恶性肿瘤中开展了试点临床试验,其中包括用源自这些LAA的合成肽对患者进行疫苗接种。这些试验结果表明,肽疫苗能够诱导有时与临床获益相关的免疫反应。这些早期临床结果很有前景,并为疫苗未来的改进提供了有价值的信息。本章将主要聚焦于讨论肽疫苗在人体系统中的临床前研究、临床试验结果以及髓系白血病疫苗治疗的未来前景。