Granziero L, Krajewski S, Farness P, Yuan L, Courtney M K, Jackson M R, Peterson P A, Vitiello A
The R.W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA.
Eur J Immunol. 1999 Apr;29(4):1127-38. doi: 10.1002/(SICI)1521-4141(199904)29:04<1127::AID-IMMU1127>3.0.CO;2-X.
Cancer-related mortality can be decreased by prevention, early detection and improved therapies. Although animal models should be used to evaluate the success of cancer therapies, their usefulness is controversial. Many cancer therapies that have cured tumors in mice have not met with similar success when attempted in humans. Current animal models rely mainly on inoculating cell lines into animals, a method that does not reproduce the natural development of the tumor, both for the kinetics of induction and the anatomical site concerned. In this study, we have used an SV40 T-antigen-transgenic mouse model of prostate cancer in which the tumor spontaneously develops orthotopically with a disease progression that closely resembles the progression of human prostate cancer. We have used this model to test the suitability of adoptive cellular immunotherapy. Transfer of naive cells obtained from a T-antigen-negative congenic animal had significant but partial effects: it prevented development of malignant tumors, leaving just minor foci of residual tumor and/or hyperplasia. Adoptive transfer of memory lymphocytes specific for T-antigen, which is a prostatic self antigen in this model, prevented tumor development and progression without affecting the morphology and function of involved tissues. Treated animals were able to breed, and their survival was greatly increased. These results strongly suggest that adoptive immunotherapy should be successful in treating early stages of human prostate cancer.
癌症相关死亡率可通过预防、早期检测和改进治疗方法来降低。尽管应使用动物模型来评估癌症治疗的成效，但其效用存在争议。许多在小鼠中治愈肿瘤的癌症治疗方法应用于人类时并未取得类似成功。当前的动物模型主要依靠将细胞系接种到动物体内，这种方法无论在诱导动力学还是相关解剖部位方面，都无法重现肿瘤的自然发展过程。在本研究中，我们使用了一种前列腺癌的SV40 T抗原转基因小鼠模型，其中肿瘤在原位自发发展，疾病进展与人类前列腺癌的进展极为相似。我们利用该模型测试过继性细胞免疫疗法的适用性。从T抗原阴性同基因动物获取的幼稚细胞转移产生了显著但部分的效果：它阻止了恶性肿瘤的发展，仅留下微小的残余肿瘤灶和/或增生。对该模型中作为前列腺自身抗原的T抗原具有特异性的记忆淋巴细胞进行过继性转移，可阻止肿瘤发展和进展，且不影响相关组织的形态和功能。接受治疗的动物能够繁殖，其存活率大幅提高。这些结果有力地表明，过继性免疫疗法在治疗人类前列腺癌早期阶段应会取得成功。
