Treon S P, Raje N, Anderson K C
Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Semin Oncol. 2000 Oct;27(5):598-613.
The use of immunotherapy to treat patients with plasma cell dyscrasias (PCD) such as multiple myeloma (MM) and Waldenström's macroglobulinemia (WM) has gained enormous interest in recent years, with considerable efforts being mounted by many investigators. These efforts have included the use of serotherapy (antibody-mediated immunotherapy), vaccination strategies aimed at inducing allogeneic as well as autologous anti-MM immunity, and the use of donor lymphocyte infusions (DLIs). A number of cell surface antigens on malignant plasma cells and/or B cells in MM and/or WM patients have been proposed for use in tumor cell-targeted serotherapy, including immunoglobulin idiotype, CD19, CD20, CD38, CD54, CD138, HM1.24, and MUC1 core protein. Ongoing clinical trials are examining serotherapy targeting CD20 (in MM and WM) and CD38 (in MM), with early reports of responses to the anti-CD20 monoclonal antibody (mAb) Rituximab (Genentech, South San Francisco, CA) in patients with WM and certain patients with MM. The use of agents to induce MM- and WM-selective antigens for targeting in serotherapy has been proposed based on studies demonstrating the upregulation of CD20 by interferon-gamma (IFN-gamma), and of MUC1 core protein by dexamethasone (DEX) on malignant plasma cells. Strategies to induce allogeneic anti-MM immunity have included immunization of the marrow donor to idiotypic protein, as well as DLI. In addition, proposed immunization strategies aimed at inducing autologous immunity include vaccination with dendritic cells pulsed with MM antigens, MM cell-dendritic cell fusions, carrier-linked idiotype protein, catalytic subunit of telomerase, or DNA encoding for single-chain variable fragments (scFv) linked to a carrier protein gene. Whole tumor vaccination strategies are also being examined and include the use of MM cells transfected and/or stimulated with cytokines, costimulatory molecules, or CD40 ligand. Finally, potential obstacles to the use of immunotherapy, including the presence of resistance antigens on MM and WM tumor cells, are discussed.
近年来，使用免疫疗法治疗浆细胞异常增生症（PCD）患者，如多发性骨髓瘤（MM）和华氏巨球蛋白血症（WM），已引起了极大的关注，许多研究人员付出了相当大的努力。这些努力包括血清疗法（抗体介导的免疫疗法）、旨在诱导同种异体以及自体抗MM免疫的疫苗接种策略，以及供体淋巴细胞输注（DLI）的使用。已提出将MM和/或WM患者恶性浆细胞和/或B细胞上的多种细胞表面抗原用于肿瘤细胞靶向血清疗法，包括免疫球蛋白独特型、CD19、CD20、CD38、CD54、CD138、HM1.24和MUC1核心蛋白。正在进行的临床试验正在研究针对CD20（在MM和WM中）和CD38（在MM中）的血清疗法，早期报告显示，WM患者和某些MM患者对抗CD20单克隆抗体（mAb）利妥昔单抗（基因泰克公司，加利福尼亚州南旧金山）有反应。基于研究表明干扰素-γ（IFN-γ）可上调恶性浆细胞上的CD20，地塞米松（DEX）可上调MUC1核心蛋白，已提出使用药物诱导MM和WM选择性抗原用于血清疗法靶向。诱导同种异体抗MM免疫的策略包括对骨髓供体进行独特型蛋白免疫以及DLI。此外，旨在诱导自体免疫的拟议疫苗接种策略包括用MM抗原脉冲处理的树突状细胞、MM细胞-树突状细胞融合体、载体连接的独特型蛋白、端粒酶催化亚基或与载体蛋白基因连接的单链可变片段（scFv）编码DNA进行疫苗接种。全肿瘤疫苗接种策略也在研究中，包括使用经细胞因子、共刺激分子或CD40配体转染和/或刺激的MM细胞。最后，讨论了免疫疗法使用中的潜在障碍，包括MM和WM肿瘤细胞上存在抗性抗原。
