Eisenstein T K, Bushnell B, Meissler J J, Dalal N, Schafer R, Havas H F
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Med Oncol. 1995 Jun;12(2):103-8. doi: 10.1007/BF01676710.
An attenuated strain of Salmonella typhimurium, SL3235, developed as a prototypic typhoid vaccine, is shown to retard growth of a murine plasmacytoma, TEPC-183, and to prolong survival of tumor-bearing mice. Live salmonella, but not acetone-killed organisms, had antitumor activity. The immunotherapeutic effect was demonstrable when the tumor was injected intralesionally or intraperitoneally. Increased survival, longer mean time to death, and retardation of tumor growth were found when the salmonella were given intralesionally as late as the sixth day post-tumor injection. Timing of salmonella inoculation, as well as the salmonella dose, had an effect on treatment efficacy. Injection of salmonella intraperitoneally exerted a strong antitumor effect when given as late as the third day post-tumor inoculation. The highest dose (2 x 10(6)) of salmonella was less effective than doses 10- or 100-fold lower. TEPC-183 plasmacytoma is rapidly growing and highly immunosuppressive, so the ability of the salmonella to exert therapeutic activity against it is a measure of the potency of the vaccine. These observations are of interest, as they show that a genetically engineered, avirulent strain of Salmonella has immunotherapeutic properties similar to those of BCG and other biological response modifiers, and might have clinical potential as an antitumor agent.
作为原型伤寒疫苗而研发的鼠伤寒沙门氏菌减毒株SL3235，已显示出可抑制小鼠浆细胞瘤TEPC - 183的生长，并延长荷瘤小鼠的生存期。活的沙门氏菌具有抗肿瘤活性，而丙酮灭活的菌体则没有。当肿瘤通过瘤内注射或腹腔注射时，免疫治疗效果是可证实的。当在肿瘤注射后第6天瘤内给予沙门氏菌时，发现荷瘤小鼠生存期延长、平均死亡时间延长以及肿瘤生长受到抑制。沙门氏菌接种的时间以及接种剂量对治疗效果均有影响。在肿瘤接种后第3天腹腔注射沙门氏菌，即使很晚给予也能发挥强大的抗肿瘤作用。最高剂量（2×10⁶）的沙门氏菌比低10倍或100倍的剂量效果要差。TEPC - 183浆细胞瘤生长迅速且具有高度免疫抑制性，因此沙门氏菌对其发挥治疗活性的能力是衡量该疫苗效力的一个指标。这些观察结果很有意思，因为它们表明一种基因工程改造的无毒沙门氏菌菌株具有与卡介苗和其他生物反应调节剂相似的免疫治疗特性，并且可能具有作为抗肿瘤药物的临床潜力。
