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利用与前列腺抗原反应的雌性小鼠来源的 T 细胞进行前列腺癌的过继细胞治疗。

Adoptive cell therapy of prostate cancer using female mice-derived T cells that react with prostate antigens.

机构信息

Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.

出版信息

Cancer Immunol Immunother. 2011 Mar;60(3):349-60. doi: 10.1007/s00262-010-0939-5. Epub 2010 Nov 19.

Abstract

In this study, we report a novel treatment strategy that could potentially be used to improve efficacy of adoptive cell therapy for patients with prostate cancer. We show that female C57BL/6 mice are able to effectively reject two syngeneic prostate tumors (TRAMP-C2 and RM1) in a T cell-dependent manner. The protective antitumor immunity appears to primarily involve T cell responses reactive against general prostate tumor/tissue antigens, rather than simply to male-specific H-Y antigen. For the first time we show that adoptive transfer of lymphocytes from TRAMP-C2-primed or naïve female mice effectively control prostate tumor growth in male mice, when combined with host pre-conditioning (i.e., non-myeloablative lymphodepletion) and IL-2 administration. No pathological autoimmune response was observed in the treated tumor-bearing male mice. Our studies provide new insights regarding the immune-mediated recognition of male-specific tissue, such as the prostate, and may offer new immunotherapy treatment strategies for advanced prostate cancer.

摘要

在这项研究中,我们报告了一种新的治疗策略,可能有助于提高过继性细胞疗法治疗前列腺癌患者的疗效。我们发现,雌性 C57BL/6 小鼠能够以 T 细胞依赖的方式有效排斥两种同基因前列腺肿瘤(TRAMP-C2 和 RM1)。这种保护性抗肿瘤免疫主要涉及针对一般前列腺肿瘤/组织抗原的 T 细胞反应,而不仅仅是针对男性特异性 H-Y 抗原。我们首次表明,从 TRAMP-C2 致敏或未致敏的雌性小鼠中过继转移淋巴细胞,与宿主预处理(即非清髓性淋巴细胞耗竭)和 IL-2 给药联合使用,可有效控制雄性小鼠的前列腺肿瘤生长。在接受治疗的荷瘤雄性小鼠中未观察到病理性自身免疫反应。我们的研究提供了关于对男性特异性组织(如前列腺)的免疫介导识别的新见解,并可能为晚期前列腺癌提供新的免疫治疗策略。

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本文引用的文献

1
Levees of immunological tolerance.免疫耐受的堤坝。
Nat Immunol. 2010 Jan;11(1):3-6. doi: 10.1038/ni.1833. Epub 2009 Dec 17.

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