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将人类实体瘤植入免疫缺陷(SCID)小鼠后的TALL-104细胞疗法。

TALL-104 cell therapy of human solid tumors implanted in immunodeficient (SCID) mice.

作者信息

Cesano A, Visonneau S, Santoli D

机构信息

Wistar Institute, Philadelphia, PA 19104, USA.

出版信息

Anticancer Res. 1998 Jul-Aug;18(4A):2289-95.

PMID:9703868
Abstract

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.

摘要

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。

相似文献

1
TALL-104 cell therapy of human solid tumors implanted in immunodeficient (SCID) mice.将人类实体瘤植入免疫缺陷(SCID)小鼠后的TALL-104细胞疗法。
Anticancer Res. 1998 Jul-Aug;18(4A):2289-95.
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Cell therapy of a highly invasive human breast carcinoma implanted in immunodeficient (SCID) mice.对植入免疫缺陷(SCID)小鼠体内的高侵袭性人类乳腺癌进行细胞治疗。
Clin Cancer Res. 1997 Sep;3(9):1491-500.
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Severe combined immunodeficient-hu model of human prostate cancer metastasis to human bone.人前列腺癌转移至人骨的严重联合免疫缺陷-人模型
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Antitumor efficacy of a human major histocompatibility complex nonrestricted cytotoxic T-cell line (TALL-104) in immunocompetent mice bearing syngeneic leukemia.人主要组织相容性复合体非限制性细胞毒性T细胞系(TALL-104)对同基因白血病免疫活性小鼠的抗肿瘤疗效。
Cancer Res. 1996 Oct 1;56(19):4444-52.
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Treatment of experimental glioblastoma with a human major histocompatibility complex nonrestricted cytotoxic T cell line.用人主要组织相容性复合体非限制性细胞毒性T细胞系治疗实验性胶质母细胞瘤。
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Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer.TALL-104细胞用于难治性转移性乳腺癌患者的I期试验。
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Differential effect of high doses versus low doses of interleukin-12 on the adoptive transfer of human specific cytotoxic T lymphocyte in autologous lung tumors engrafted into severe combined immunodeficiency disease-nonobese diabetic mice: relation with interleukin-10 induction.高剂量与低剂量白细胞介素-12对移植到重症联合免疫缺陷病-非肥胖糖尿病小鼠体内的自体肺肿瘤中人特异性细胞毒性T淋巴细胞过继转移的不同影响:与白细胞介素-10诱导的关系
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The human leukemic T-cell line, TALL-104, is cytotoxic to human malignant brain tumors and traffics through brain tissue: implications for local adoptive immunotherapy.人白血病T细胞系TALL-104对人恶性脑肿瘤具有细胞毒性,并可穿过脑组织:对局部过继性免疫治疗的意义。
Cancer Res. 2000 Oct 15;60(20):5731-9.

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