Immunotherapy to Mitigate the Negative Effects of Alcohol on Cancer Progression

减轻酒精对癌症进展的负面影响的免疫疗法

基本信息

批准号：
8795141
负责人：
Hui Zhang
金额：
$ 17.72万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2016-07-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8795141
关键词：
4T1 Address Adult Affect Afghanistan Age-Years Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Biomedical Research CD8B1 gene Cancer Control Cancer Patient Cell Count Cells Cessation of life Chronic Clinical Trials Complex Cutaneous Melanoma Data Development Epidemiology Estrogens Exploratory/Developmental Grant Frequencies General Population Goals Growth Health Heavy Drinking Human IL2RA gene Immune Immune response Immune system Immunity Immunotherapeutic agent Immunotherapy Incidence Interferons Interleukin-15 Iraq Knowledge Lead Link Location Malignant Neoplasms Mediating Memory Methods Military Personnel Modeling Mus Myelogenous National Institute on Alcohol Abuse and Alcoholism Neoplasm Metastasis Patients Pharmaceutical Preparations Phase Phenotype Play Production Regimen Regulatory T-Lymphocyte Research Risk Role Services Skin Cancer Suppressor-Effector T-Lymphocytes T-Cell Proliferation T-Lymphocyte Testing The Sun Therapeutic Translating Work alcohol effect attributable mortality base cancer immunotherapy cancer therapy cancer type chronic alcohol ingestion combat drinking drinking water immunoregulation interleukin-15 receptor malignant breast neoplasm melanoma member novel novel therapeutics problem drinker receptor response statistics subcutaneous treatment effect tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): Alcohol abuse is a worldwide problem. Chronic abuse of alcohol leads to a compromised immune system, which is one factor that can increase the incidence of cancer. This is supported by epidemiological evidence indicating that chronic alcohol consumption not only increases the incidence of cancer, including melanoma, but also decreases the survival of cancer patients. Cancer immunotherapy is one of the most promising methods to control tumor progression and extend survival of cancer patients. However, there is a large gap in knowledge as to how chronic alcohol consumption affects antitumor immunity, and this severely hampers the development of effective immunotherapeutic approaches to treat cancer in people who have immune deficits due to chronic alcohol abuse. The objective of this application is to evaluate a novel immunotherapeutic approach to restore and augment antitumor immune responses that lead to increased survival of hosts with melanoma and enhance alcohol's antimetastatic activity against melanoma. The central hypothesis of this application is that augmenting and sustaining CD8+ T numbers and functions will mitigate the negative effects caused by the alcohol/melanoma interaction and result in increased survival of hosts bearing s.c. melanoma and in enhancement of the antimetastatic effect associated with alcohol consumption. To accomplish the objectives of this application the following aims will be pursued: 1) Determine the effect and immune mechanism(s) of a unique IL-15/IL15 receptor complex with and without sunitinib, a drug that inhibits myeloid derived suppressor cells and T regulatory cells, to inhibit growth and increase survival of hosts that drink alcohol chronically ad that are injected with melanoma tumors. Four sub-aims will examine the mechanism(s) underlying these effects. 2) Determine the specific effects of this treatment on melanoma metastasis. This research will greatly enhance understanding of the immune mechanisms involved in the interplay between chronic alcohol consumption and melanoma progression, and significantly advance progress toward using this immunotherapy to treat alcohol abusing patients with melanoma. This approach has the potential of being quickly translated into human clinical trials for alcohol abusing patients with melanoma and potentially other types of cancer and especially for those patients with immune deficits.

描述（由申请人提供）：酗酒是一个世界性问题。长期酗酒会导致免疫系统受损，这是增加癌症发病率的因素之一。流行病学证据表明，长期饮酒不仅会增加癌症（包括黑色素瘤）的发病率，还会降低癌症患者的生存率。癌症免疫疗法是控制肿瘤进展和延长癌症患者生存期的最有前途的方法之一。然而，对于长期饮酒如何影响抗肿瘤免疫力，人们的认识存在很大差距，这严重阻碍了有效免疫治疗方法的开发，以治疗因长期酗酒而出现免疫缺陷的人的癌症。本申请的目的是评估一种新的免疫治疗方法，以恢复和增强抗肿瘤免疫反应，从而提高黑色素瘤宿主的生存率，并增强酒精对黑色素瘤的抗转移活性。本申请的中心假设是，增加和维持 CD8+ T 数量和功能将减轻酒精/黑色素瘤相互作用引起的负面影响，并导致皮下携带病毒的宿主的存活率增加。黑色素瘤和增强与饮酒相关的抗转移作用。为了实现本申请的目标，将追求以下目标：1) 确定独特的 IL-15/IL15 受体复合物在有或没有舒尼替尼的情况下的作用和免疫机制，舒尼替尼是一种抑制骨髓源性抑制细胞和 T 细胞的药物。调节细胞，抑制长期饮酒和注射黑色素瘤的宿主的生长并提高其存活率。四个子目标将研究这些影响背后的机制。 2) 确定该治疗对黑色素瘤转移的具体效果。这项研究将极大地增进对慢性饮酒与黑色素瘤进展之间相互作用的免疫机制的理解，并显着推进使用这种免疫疗法治疗患有黑色素瘤的酗酒患者的进展。这种方法有可能迅速转化为针对患有黑色素瘤和潜在其他类型癌症的酗酒患者，特别是那些免疫缺陷患者的人体临床试验。