TREATMENT OF INDOLENT B CELL LYMPHOMA & CLL PATIENTS W/ HEAT SHOCK PR

我们的工作已经证明了热休克蛋白（HSP）在癌症免疫反应中的关键作用。 它表明：从癌症中纯化的HSP制剂可用于多种预先存在的啮齿动物癌症的免疫治疗，包括原发性和微转移性癌症; HSP疫苗接种是精确的癌症特异性的，即只有当用作HSP来源的癌症与用于攻击的癌症相同时才能看到保护。 这些发现得到了独立的证实。这些观察结果的结构基础在于以下发现：（i）HSP本身不是免疫原性的，但伴侣肽是免疫原性的;（ii）从HSP制剂中去除肽消除了它们的免疫原性;（iii）与来自一种肿瘤的HSP相关的抗原肽不同于与其它肿瘤相关的抗原肽;（iv）HSP-肽复合物引发免疫的机制涉及由巨噬细胞和树突细胞重新呈递HSP-伴侣肽。本文提出的研究将继续使用癌源性热休克蛋白70免疫治疗B细胞淋巴瘤。 这些肿瘤重新提出了解决癌症免疫治疗中关键问题的独特机会：其独特性源于它们表达个体癌症特异性标志物独特型的事实以及免疫干预在B淋巴瘤中的已证实作用。

Our work has demonstrated a key role for Heat Shock Proteins (HSPs) in immune response to cancer. It has shown that: HSP preparations purified from cancers can be used for immunotherapy of a wide variety of pre-existing rodent cancers, both primary and micro-metastatic; HSP-vaccination is exquisitely cancer-specific, i.e. protection is seen only if the cancer used as the source of HSPs is the same as the one used for challenge. These findings have been independently confirmed. The structural basis of these observations lies in the discoveries that (i) HSPs are not immunogenic per se, but chaperoned peptides are; (ii) removal of peptides from HSP preparations ablates their immunogenicity (iii) antigenic peptides associated with HSPs from one tumor are distinct from those associated with other tumors; (iv) the mechanism whereby the HSP-peptide complexes elicit immunity involves re-presentation of HSP-chaperoned peptides by macrophages and dendritic cells. The studies proposed here will pursue the use of cancer-derived hsp70 for immunotherapy of B cell lymphoma. These tumors re-present a unique opportunity to address key questions in cancer immunotherapy: the uniqueness derives from the fact that they express an individually-cancer-specific marker, the idiotype and from the proven role of immunological intervention in B lymphoma.