Verbik D, Joshi S
UNIV NEBRASKA,MED CTR,DEPT CELL BIOL & ANAT,OMAHA,NE 68198.
Int J Oncol. 1995 Aug;7(2):205-23. doi: 10.3892/ijo.7.2.205.
Conventional cancer therapies such as surgery, chemotherapy and/or radiotherapy, are not always successful in providing long-term survival for cancer patients. One of the major problems with conventional cancer therapies is their inability to eradicate residual/metastatic tumor cells that are resistant to therapy. Therefore, it is necessary to develop new methods for treating such cancer cells in order to improve the clinical outcome of these patients. Despite antitumor effector mechanisms working against cancer cells in the host's body, tumor-cell-induced immunosuppression and or antigenic modulation by the tumor cells often help tumor cells escape host defense mechanisms. Therefore, one approach for treating residual cancer would be to enhance the host's own immunological/antitumor defense mechanisms. Immune cells that have a significant role in mediating antitumor responses include: T lymphocytes; natural killer (NK) cells; macrophages; and B lymphocytes. The ability of these immune cells to effectively destroy malignant cells is carefully governed by chemical mediators in the form of proteins otherwise known as cytokines. Many cytokines (interleukins, interferons, and tumor necrosis factor) have been shown to enhance in vitro and in vivo effector cell antitumor cytotoxic activities. Utilization of cytokines in conjunction with effector cells can also mediate significant antitumor responses in both animal models and cancer patients. One of the major problems associated with systemic treatment with cytokines is the development of dose limiting toxicities. Currently, attempts to reduce this problem include developing techniques to allow for the preferential release of cytokines in proximity to the tumor cell. In this regard, effector cells or tumor cells that have been genetically engineered to secrete cytokine(s) may be useful in localizing an immune response, preferably at the tumor site. Clinical trial using cytokine gene transfected cells for treating cancer are currently under investigation. With the availability of recombinant lymphokines and with our ability to genetically modify effector cells and tumor cells this hopefully will allow us to improve current therapeutic modalities for treating cancer.
传统的癌症治疗方法，如手术、化疗和/或放疗，在为癌症患者提供长期生存方面并不总是成功的。传统癌症治疗方法的主要问题之一是它们无法根除对治疗有抗性的残留/转移性肿瘤细胞。因此，有必要开发新的方法来治疗此类癌细胞，以改善这些患者的临床结局。尽管宿主体内存在针对癌细胞的抗肿瘤效应机制，但肿瘤细胞诱导的免疫抑制和/或肿瘤细胞的抗原调节常常有助于肿瘤细胞逃避宿主防御机制。因此，治疗残留癌症的一种方法是增强宿主自身的免疫/抗肿瘤防御机制。在介导抗肿瘤反应中起重要作用的免疫细胞包括：T淋巴细胞；自然杀伤（NK）细胞；巨噬细胞；和B淋巴细胞。这些免疫细胞有效破坏恶性细胞的能力受到以蛋白质形式存在的化学介质（即细胞因子）的严格调控。许多细胞因子（白细胞介素、干扰素和肿瘤坏死因子）已被证明可增强体外和体内效应细胞的抗肿瘤细胞毒性活性。细胞因子与效应细胞联合使用也可在动物模型和癌症患者中介导显著的抗肿瘤反应。与细胞因子全身治疗相关的主要问题之一是出现剂量限制性毒性。目前，减少这一问题的尝试包括开发技术，使细胞因子在肿瘤细胞附近优先释放。在这方面，经过基因工程改造以分泌细胞因子的效应细胞或肿瘤细胞可能有助于定位免疫反应，最好是在肿瘤部位。目前正在研究使用细胞因子基因转染细胞治疗癌症的临床试验。随着重组淋巴因子的可得性以及我们对效应细胞和肿瘤细胞进行基因改造的能力，这有望使我们改进当前治疗癌症的方法。
