Salmon S E, Durie B G, Young L, Liu R M, Trown P W, Stebbing N
J Clin Oncol. 1983 Mar;1(3):217-25. doi: 10.1200/JCO.1983.1.3.217.
Clonogenic tumor cells from fresh biopsies of human cancers were cultivated in vitro and tested for sensitivity by continuous exposure to pharmacologically achievable concentrations of either of two highly purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D) prepared by recombinant DNA methods. The interferons were compared on a weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and 800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A, and in 16% of the 71 tumors tested against IFN-alpha D. Of the tumor types with at least ten samples tested against IFN-alpha A, the percentage of cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer (50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%), adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of control or less) was observed in 18.7% of all tumors tested against IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro inhibition of growth with IFN-alpha A. Although a smaller number of tumors (71) were tested against IFN-alpha D on a weight basis, it appeared, in general, to be slightly less active than IFN-alpha A (p less than 0.01), and only 8% of tumors tested exhibited marked inhibition over the same dosage range of interferon. Comparison of the dose-response curves for the 68 tumors tested simultaneously against both interferons did not reveal marked interpatient differences in the inhibition curves, although IFN-alpha D was slightly less active overall. Tumors exhibiting at least 50% inhibition of tumor colony formation also proved to be sensitive to a significantly larger number of cytotoxic drugs (tested simultaneously) than the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha A). We conclude that the in vitro clonogenic assay may aid in targeting tumor types most likely to exhibit interferon sensitivity and assist in case selection for entry into clinical trials with cloned interferons.
从人类癌症新鲜活检样本中获取的克隆形成肿瘤细胞在体外进行培养，并通过持续暴露于两种经重组DNA方法制备的高度纯化的人白细胞干扰素亚型（IFN-αA和IFN-αD）药理学可达到的浓度来测试其敏感性。将干扰素按重量比在0.4和4.0 ng/ml的浓度下进行比较（对于IFN-αA相当于80和800单位的干扰素活性，对于IFN-αD相当于2.0和20单位）。在针对IFN-αA测试的273个肿瘤中，有38.1%观察到肿瘤集落形成单位受到抑制（对照组的50%或更低），在针对IFN-αD测试的71个肿瘤中，有16%观察到这种抑制。在针对IFN-αA测试的样本数至少为10个的肿瘤类型中，出现抑制的病例百分比如下：黑色素瘤（51.7%）、肺癌（50%）、骨髓瘤（33.4%）、卵巢癌（33.9%）、肉瘤（33.3%）、原发灶不明的腺癌（30.4%）、乳腺癌（28%）、急性白血病（30.8%）和肾癌（23%）。在针对IFN-αA测试的所有肿瘤中，有18.7%观察到更显著的抑制（对照组的30%或更低）。在测试的60个黑色素瘤中，18个（30%）在体外表现出IFN-αA对生长的显著抑制。尽管按重量比针对IFN-αD测试的肿瘤数量较少（71个），但总体上它似乎比IFN-αA活性稍低（p小于0.01），在相同剂量范围内测试的肿瘤中只有8%表现出显著抑制。对同时针对两种干扰素测试的68个肿瘤的剂量反应曲线进行比较，尽管IFN-αD总体活性稍低，但未发现患者间抑制曲线有显著差异。与未被干扰素抑制的肿瘤相比，表现出至少50%肿瘤集落形成抑制的肿瘤对大量细胞毒性药物（同时测试）也更敏感（针对IFN-αA，p小于0.0001）。我们得出结论，体外克隆形成试验可能有助于确定最可能表现出干扰素敏感性的肿瘤类型，并协助选择进入克隆干扰素临床试验的病例。
