Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study

Ajay V. Maker MD; Giao Q. Phan MD; Peter Attia MD; James C. Yang MD; Richard M. Sherry MD; Suzanne L. Topalian MD; Udai S. Kammula MD; Richard E. Royal MD; Leah R. Haworth RN; Catherine Levy RN; David Kleiner MD; Sharon A. Mavroukakis RN; Michael Yellin MD; Steven A. Rosenberg MD; PhD

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Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study

机译：细胞毒性T淋巴细胞相关抗原4阻断和白介素治疗的患者的肿瘤消退和自身免疫性：I / II期研究

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Cytotoxic T lymphocyte–associated antigen (CTLA)-4 can inhibit T-cell responses and is involved in tolerance against self antigens. We previously reported autoimmune manifestations and objective cancer regressions in patients with metastatic melanoma treated with CTLA-4 blockade. The possibility of activating tumor-reactive T cells while removing inhibitory activity with CTLA-4 blockade has stimulated interest in using anti–CTLA-4 antibodies in combination with other cancer immunotherapies to improve clinical outcomes. In this study, we assessed the antitumor activity and autoimmune toxicity of CTLA-4 blockade in combination with an immune-activating stimulus, interleukin (IL)-2, in patients with metastatic melanoma.

机译：细胞毒性T淋巴细胞相关抗原（CTLA）-4可以抑制T细胞反应，并参与对自身抗原的耐受性。我们先前曾报道接受CTLA-4阻断治疗的转移性黑色素瘤患者的自身免疫表现和客观的癌症消退。激活肿瘤反应性T细胞，同时消除CTLA-4阻滞抑制活性的可能性，激发了人们对使用抗CTLA-4抗体与其他癌症免疫疗法结合以改善临床结果的兴趣。在这项研究中，我们评估了转移性黑色素瘤患者中CTLA-4阻断剂与免疫激活刺激物白介素（IL）-2的联合抗肿瘤活性和自身免疫毒性。

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来源
《Annals of Surgical Oncology》 |2005年第12期|1005-1016|共12页
作者
Ajay V. Maker MD; Giao Q. Phan MD; Peter Attia MD; James C. Yang MD; Richard M. Sherry MD; Suzanne L. Topalian MD; Udai S. Kammula MD; Richard E. Royal MD; Leah R. Haworth RN; Catherine Levy RN; David Kleiner MD; Sharon A. Mavroukakis RN; Michael Yellin MD; Steven A. Rosenberg MD; PhD;
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Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

Medarex Inc. 519 Route 173 West Bloomsbury New Jersey 08804;

Surgery Branch National Cancer Institute National Institutes of Health CRC Room 3-3940 10 Center Drive MSC 1201 Bethesda Maryland 20814;

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正文语种 eng
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关键词
Cytotoxic T lymphocyte-associated antigen 4; Interleukin 2; Melanoma; Autoimmunity;

机译：细胞毒性T淋巴细胞相关抗原4;白介素2;黑素瘤;自身免疫;

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专利

1. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. [J] . Maker AV, Phan GQ, Attia P, Annals of surgical oncology . 2005,第12期

机译：I / II期研究：接受细胞毒性T淋巴细胞相关抗原4阻断和白介素2治疗的患者的肿瘤消退和自身免疫。
2. T-Cell Therapy Using Interleukin-21-Primed Cytotoxic T-Cell Lymphocytes Combined With Cytotoxic T-Cell Lymphocyte Antigen-4 Blockade Results in Long-Term Cell Persistence and Durable Tumor Regression [J] . Chapuis Aude G., Roberts Ilana M., Thompson John A., Journal of Clinical Oncology . 2016,第31期

机译：使用白介素21为主的细胞毒性T细胞淋巴细胞与细胞毒性T细胞淋巴细胞抗原4结合的T细胞疗法可导致长期的细胞持久性和持久的肿瘤消退
3. Tumor Regression and Autoimmunity in CytotoxicT Lymphocyte–Associated Antigen 4 Blockade–Treated Patients [J] . Jeffrey S. Weber MD, PhD Annals of Surgical Oncology . 2005,第12期

机译：细胞毒性T淋巴细胞相关抗原4阻断治疗患者的肿瘤消退和自身免疫
4. IN VIVO CYTOSOLIC DELIVERY OF EXOGENOUS ANTIGEN MEDIATED BY LISTERIOLYSIN O: ENHANCED CYTOTOXIC T-LYMPHOCYTE INDUCTION AND TUMOR PROTECTION [C] . M. Mandal, K.-D. Lee International symposium on controlled release of bioactive materials;Consumer diversified products conference . 2001

机译：脂溶素O介导的外源抗原的体内细胞液递送：增强的细胞毒性T淋巴细胞诱导和肿瘤保护
5. Initial study of the role of native interleukin-15 in generating tumor-specific cytotoxic T lymphocytes in a dendritic cell-mediated ex vivo system. [D] . Ye, Mulin. 2011

机译：天然白介素15在树突状细胞介导的离体系统中产生肿瘤特异性细胞毒性T淋巴细胞中的作用的初步研究。
6. Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study [O] . Ajay V. Maker, Giao Q. Phan, Peter Attia, -1

机译：细胞毒性T淋巴细胞相关抗原4阻断和白介素治疗的患者的肿瘤消退和自身免疫性：I / II期研究
7. Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study [O] . Ajay V. Maker, Giao Q. Phan, Peter Attia, 2005

机译：用细胞毒性T淋巴细胞相关抗原4封闭和白细胞介素2治疗患者的肿瘤回归和自身免疫2：I / II期研究

Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study

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