Immunity to stem cell antigens in preneoplastic gammopathy

描述（由申请方提供）：意义不明的单克隆丙种球蛋白病（MGUS）发生在4%的50岁以上人群中，代表骨髓瘤的前驱病变。虽然一些研究已经检查了对人类癌症（包括骨髓瘤）抗原的免疫应答，但对癌前病变免疫应答的性质研究较少。该应用基于我们最近的发现，即大部分MGUS患者对胚胎/癌症干细胞上表达的抗原具有自发免疫应答。在初步研究中，这些反应的检测预测疾病进展的可能性降低。本申请中研究的具体目的是1）更好地了解MGUS中这种天然存在的免疫应答; 2）进一步评价骨髓瘤患者中不存在这些应答的基础; 3）在前瞻性临床试验的背景下了解这些患者对干细胞抗原的免疫的临床和预后意义。这些研究对增强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的方法具有直接意义。公共卫生相关性：这些研究的目的是了解在没有癌症的人中自然发生的针对癌症干细胞的免疫反应的特性。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.