Cesano A, Visonneau S, Santoli D
Wistar Institute, Philadelphia, PA 19104, USA.
Anticancer Res. 1998 Jul-Aug;18(4A):2289-95.
We have developed a novel approach to adoptive therapy of cancer based on the use of a human T cell line (TALL-104) which is endowed with major histocompatibility complex non-restricted cytotoxic activity against a broad range of tumors and across several species, while sparing cells from normal tissues. The present study investigates the efficacy of TALL-104 cell therapy in severe combined immunodeficient (SCID) mice implanted with human solid tumors. The human cell lines DU-145 (prostate cancer), A549 (lung carcinoma) and WM451 (melanoma) were implanted subcutaneously (s.c.) in the flank region of the mice. Multiple intraperitoneal (i.p.) transfers of lethally irradiated TALL-104 cells into animals bearing small tumor masses (150 mg) resulted in 50-75% reduction of local tumor growth and complete prevention of pulmonary metastasis. In mice implanted s.c. with A549 cells, dramatic antitumor effects against both local and metastatic disease were observed when cell therapy was initiated after surgical excision of the primary tumor mass. In another set of experiments, the DU-145 and WM451 cells were injected intravenously (i.v.); cells disseminated aggressively in various organs and all animals died within 6-10 weeks from engraftment. However, experimental mice that received TALL-104 cell therapy i.p. daily, starting 1 week after tumor inoculation, showed longer survival and a slower tumor growth (as measured monthly by plasmatic levels of the sICAM-1 tumor marker). At necropsy 1/6 of these animals were disease free. Taken together, these data indicate the effectiveness of this novel antitumor agent in prolonging disease-free survival and controlling tumor growth and invasion.
我们开发了一种基于使用人T细胞系(TALL-104)的癌症过继性治疗新方法,该细胞系具有针对多种肿瘤和跨多个物种的主要组织相容性复合体非限制性细胞毒性活性,同时对正常组织细胞无损害。本研究调查了TALL-104细胞疗法对植入人实体瘤的严重联合免疫缺陷(SCID)小鼠的疗效。将人细胞系DU-145(前列腺癌)、A549(肺癌)和WM451(黑色素瘤)皮下植入小鼠的胁腹区域。将经致死剂量照射的TALL-104细胞多次腹腔注射到携带小肿瘤块(150毫克)的动物体内,导致局部肿瘤生长减少50%-75%,并完全预防肺转移。在皮下植入A549细胞的小鼠中,在手术切除原发性肿瘤块后开始细胞治疗时,观察到对局部和转移性疾病均有显著的抗肿瘤作用。在另一组实验中,将DU-145和WM451细胞静脉注射;细胞在各个器官中大量扩散,所有动物在移植后6-10周内死亡。然而,在肿瘤接种后1周开始每天腹腔接受TALL-104细胞治疗的实验小鼠显示出更长的生存期和更慢的肿瘤生长(每月通过血浆sICAM-1肿瘤标志物水平测量)。尸检时,这些动物中有1/6无疾病。综上所述,这些数据表明这种新型抗肿瘤药物在延长无病生存期以及控制肿瘤生长和侵袭方面是有效的。