Immunotherapy as part of combinations for the treatment of cancer.
Immunotherapy as part of combinations for the treatment of cancer.
复制标题
DOI：
10.1016/s1567-5769(03)00019-5
复制
发表时间：
2003-08
影响因子：
5.6
通讯作者：
M. Mitchell
中科院分区：
文献类型：
--
作者：
M. Mitchell
免疫疗法（生物疗法）包括诸如主动特异性免疫疗法（“癌症疫苗”）、用细胞因子的非特异性免疫刺激以及抑制由肿瘤施加或引发的抑制剂影响。正如癌症化疗开始使用单一药物并发展为联合治疗一样，免疫药物也相互结合并与化疗结合。烷化剂环磷酰胺（环磷酰胺; CY）多年来一直用于抑制啮齿类动物中的肿瘤源性抑制因子影响，并已被开发用于人类中的相同用途。CY和癌症疫苗的组合，如自体肿瘤细胞，Melacine，大型多价免疫原（LMI）和Theratope已经在人类中测试了十多年，取得了一些成功。在该用途中，CY是生物反应调节剂而不是抗肿瘤剂。在治疗小鼠浆细胞瘤中，CY延迟治疗已被证明比立即治疗更有效，可能是因为它允许宿主产生免疫力。CY和中等剂量的白细胞介素-2（IL-2）也是治疗人类黑色素瘤的有效方案。IL-2本身是组合免疫疗法的有用组分，例如与黑素瘤肽疫苗或与干扰素-α-2b（IFN-α）作为双重组合或生物化疗方案的一部分。IL-2和组胺，阻断活性氧，可能是一个更有用的组合，用于治疗黑色素瘤肝转移比IL-2单独。在这种组合中，组胺可以允许持续的、不受阻碍的溶细胞性T淋巴细胞的活性。几种不同的药物和生物制剂的组合已被用作黑色素瘤的生物化疗，但尽管有较高的即时反应率，长期生存的好处一直是微不足道的，没有理由的严重毒性。5-氟尿嘧啶（5-FU）和IFN-α或左旋咪唑的组合在结肠癌和头颈癌中具有疗效，但在这里，生物制剂充当生化调节剂。抗体和化疗的试验一直很有限。看来曲妥珠单抗（赫赛汀）加强乳腺癌的抗肿瘤治疗，也增加了这些方案的心脏毒性。
Immunotherapy (biological therapy) comprises such things as active specific immunotherapy (“cancer vaccines”), nonspecific immunostimulation with cytokines, and the inhibition of suppressor influences exerted or elicited by the tumor. Just as cancer chemotherapy began with the use of single agents and evolved into combination therapy, so immunotherapeutic agents have been combined with each other and with chemotherapy. The alkylating agent cyclophosphamide (Cytoxan; CY) has been used for many years to inhibit tumor-derived suppressor influences in rodents, and has been exploited for the same use in humans. Combinations of CY and cancer vaccines such as autologous tumor cells, Melacine, large multivalent immunogen (LMI), and Theratope have been tested with some success in humans for more than a decade. In this use, the CY is a biological response modifier rather than an antitumor agent. Delayed treatment with CY in treating mouse plasmacytomas has proved more effective than immediate treatment, probably because it allows immunity to develop in the host. CY and moderate-dose interleukin-2 (IL-2) have also been a useful regimen in treating human melanomas. IL-2 is itself a useful component of combination immunotherapy, such as with melanoma peptide vaccines, or with interferon-alfa-2b, (IFN-a), as a dual combination or part of a biochemotherapy regimen. IL-2 and histamine, to block reactive oxygen species, may be a more useful combination for treatment of liver metastases of melanoma than IL-2 alone. In this combination, the histamine may permit continued, unimpeded activity of cytolytic T lymphocytes. Several different combinations of drugs and biological agents have been used as biochemotherapy for melanoma, but although there are higher immediate response rates, the long-range survival benefits have been marginal, not justifying the severe toxicity. Combinations of 5-fluorouracil (5-FU) and IFN-a or levamisole have had efficacy in colon and head and neck cancers, but here the biological agents acted as biochemical modulators. Trials of antibodies and chemotherapy have been limited. It appears that trastuzumab (Herceptin) potentiates antitumor therapy in breast cancer and also increases the cardiotoxicity of those regimens.