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前列腺癌患者中对源自前列腺特异性抗原的肽段的特异性T细胞识别。

Specific T cell recognition of peptides derived from prostate-specific antigen in patients with prostate cancer.

作者信息

Alexander R B, Brady F, Leffell M S, Tsai V, Celis E

机构信息

Urology Section, U.S. Department of Veterans Affairs Maryland Health Care System, Baltimore, Maryland, USA.

出版信息

Urology. 1998 Jan;51(1):150-7. doi: 10.1016/s0090-4295(97)00480-9.

Abstract

OBJECTIVES

To determine if proteins known to be expressed by both benign and malignant prostate epithelium can be recognized by T cells from patients with prostate cancer. We examined 7 HLA-A2 patients with prostate cancer for evidence of T cell reactivity with prostate-specific antigen (PSA).

METHODS

Four peptides derived from PSA were chemically synthesized and shown to bind to HLA-A2. As a control, we also examined the immunogenic influenza matrix peptide Flu58-66 that binds to HLA-A2. These peptides were used to stimulate peripheral blood lymphocytes by in vitro stimulation.

RESULTS

In 1 patient, specific recognition of peptide PSA141-150 was observed. The remaining 6 patients had no reactivity with any PSA-derived peptide. The T cell line with specific recognition of peptide PSA141-150 failed to recognize an autologous B cell blast line expressing endogenous PSA following infection with a recombinant PSA vaccinia virus construct. Three of the 7 patients demonstrated specific reactivity with Flu58-66.

CONCLUSIONS

We found specific recognition of one PSA-derived peptide in 1 patient of 7 with prostate cancer. The peptide-specific lymphocyte cell line did not recognize endogenous PSA, suggesting that the peptide may not be produced by prostate cancer cells producing PSA. Specific recognition of PSA peptides was not common in our patients with prostate cancer. Whether such activity can be induced by vaccination strategies or can be therapeutic in men with established prostate cancer remains to be demonstrated.

摘要

目的

确定已知由良性和恶性前列腺上皮表达的蛋白质是否能被前列腺癌患者的T细胞识别。我们检测了7例HLA - A2型前列腺癌患者,以寻找T细胞与前列腺特异性抗原(PSA)发生反应的证据。

方法

化学合成了4种源自PSA的肽段,并证明它们能与HLA - A2结合。作为对照,我们还检测了与HLA - A2结合的免疫原性流感基质肽Flu58 - 66。这些肽段用于通过体外刺激来刺激外周血淋巴细胞。

结果

在1例患者中观察到对肽段PSA141 - 150的特异性识别。其余6例患者对任何源自PSA的肽段均无反应。对肽段PSA141 - 150具有特异性识别的T细胞系,在感染重组PSA痘苗病毒构建体后,未能识别表达内源性PSA的自体B细胞母细胞系。7例患者中有3例对Flu58 - 66表现出特异性反应。

结论

我们在7例前列腺癌患者中的1例中发现了对一种源自PSA的肽段的特异性识别。肽段特异性淋巴细胞系未识别内源性PSA,这表明该肽段可能不是由产生PSA的前列腺癌细胞产生的。在我们的前列腺癌患者中,对PSA肽段的特异性识别并不常见。这种活性是否能通过疫苗接种策略诱导产生,或者对已确诊的前列腺癌男性患者是否具有治疗作用,仍有待证实。

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