Immunity to stem cell antigens in preneoplastic gammopathy

描述(由申请人提供)：未确定意义的单克隆性伽马病(MGUS)发生在4%的50岁以上的人群中，是骨髓瘤的前驱病变。虽然一些研究已经检测了包括骨髓瘤在内的人类癌症对抗原的免疫反应，但对癌前病变的免疫反应的性质研究较少。这一应用建立在我们最近的发现基础上，即很大比例的MGUS患者对胚胎/癌症干细胞上表达的抗原具有自发免疫反应。在初步研究中，对这些反应的检测预测了疾病进展的可能性降低。本申请中研究的具体目标是1)更好地了解MGUS中这种自然发生的免疫反应；2)进一步评估骨髓瘤患者没有这些反应的基础；3)在前瞻性临床试验的背景下，了解对干细胞抗原的免疫在这些患者中的临床和预后意义。这些研究对提高宿主对骨髓瘤干细胞的免疫力以及利用宿主反应的特性进行风险评估和癌症早期检测具有直接意义。公共卫生相关性：这些研究的目标是了解非癌症患者对癌症干细胞的自然免疫反应的特性。利用这种反应可能对预防癌症(如骨髓瘤)很重要。

DESCRIPTION (provided by applicant): Monoclonal gammopathy of undetermined significance (MGUS) occurs in 4% of the population over 50 years old and represents a precursor lesion to myeloma. Although several studies have examined the immune response to antigens in human cancer including myeloma, the nature of immune response against preneoplastic lesions is less studied. This application builds on our recent findings that a large proportion of patients with MGUS harbor spontaneous immune responses against antigens expressed on embryonal / cancer stem cells. In preliminary studies, the detection of these responses predicted reduced probability of disease progression. The specific objectives of the studies in this application are 1) to better understand this naturally occurring immune response in MGUS; 2) to further evaluate the basis of the absence of these responses in myeloma patients; and 3) to understand the clinical and prognostic significance of immunity to stem cell antigens in these patients in the context of a prospective clinical trial. These studies have direct implications for approaches to boost host immunity against myeloma stem cells and harnessing properties of host response for risk assessment and early detection of cancer. PUBLIC HEALTH RELEVANCE: The goal of these studies is to understand the properties of naturally occurring immune responses against cancer stem cells in people without cancer. Harnessing such responses may be important for prevention of cancer, such as myeloma.