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向黑猩猩输注经致敏的自体培养T细胞的临床效果。

Clinical effects of infusions into chimpanzees of primed autologous cultured T-cells.

作者信息

Slease R B, Strong D M, Gawith K E, Bonnard G D

出版信息

J Natl Cancer Inst. 1981 Aug;67(2):489-93.

PMID:6973657
Abstract

As a model to study the possible early side effects of cultured T-cells (CTC) as a potential for adoptive cellular immunotherapy of human tumors, chimpanzees received iv infusions of 10(9) autologous, mixed lymphocyte culture-primed CTC. Complete blood counts, urinalyses, chest X-rays, blood chemistries, and serum immunoelectrophoresis were normal, and serologic studies were negative throughout the 3 weeks of observation. Serial transaminase levels were followed in 2 chimps, and mild increases in serum glutamic-oxaloacetic transaminase were seen in both and serum glutamic-pyruvic transaminase in 1 at 24 hours following each CTC infusion, but the levels returned to normal within 7 days. A liver biopsy specimen was normal. Fluorescence-activated cell sorter analysis of cells incubated with day 28 serum revealed weak labeling of only phytohemagglutinin (PHA)-stimulated lymphoblasts and of CTC, suggesting that a weak anti-PHA antibody was generated. These studies indicate that infusions of autologous, in vitro-primed CTC are accompanied by little clinical toxicity in the chimp model but that they may be weakly immunogenic.

摘要

作为研究培养的T细胞(CTC)作为人类肿瘤过继性细胞免疫疗法潜力的可能早期副作用的模型,黑猩猩接受了静脉输注10⁹个自体混合淋巴细胞培养致敏的CTC。在整个3周的观察期内,全血细胞计数、尿液分析、胸部X光、血液化学和血清免疫电泳均正常,血清学研究为阴性。对2只黑猩猩进行了连续转氨酶水平监测,每次输注CTC后24小时,两只黑猩猩的血清谷草转氨酶均有轻度升高,1只黑猩猩的血清谷丙转氨酶也有升高,但这些水平在7天内恢复正常。肝脏活检标本正常。用第28天血清孵育的细胞进行荧光激活细胞分选分析显示,仅植物血凝素(PHA)刺激的淋巴母细胞和CTC有弱标记,提示产生了弱抗PHA抗体。这些研究表明,在黑猩猩模型中,自体体外致敏的CTC输注几乎没有临床毒性,但可能具有弱免疫原性。

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