Host-Tumor Cell Interactions in Myeloma: Therapeutic Applications

2001年，多发性骨髓瘤（MM）在美国影响了14,400名新患者，患者总数为50,000人，尽管采用常规和高剂量治疗，但仍然无法治愈。因此，迫切需要针对肿瘤细胞及其微环境的独特靶点的新型治疗干预措施。当前提案“骨髓瘤中宿主-肿瘤细胞相互作用：治疗应用”的主要目标是开发针对宿主-肿瘤细胞相互作用的新疗法，以克服耐药性，实现MM的长期无病生存和潜在治愈。该项目建立并扩展了先前资助期的进展，现在有三个主要目标。首先，我们将尝试在治疗上利用异体供体免疫应答对MM的相互作用，并为新疗法确定目标抗原（Ritz项目）。其次，我们将尝试增强自体抗- mm

Multiple myeloma (MM) affected 14,400 new individuals in the United States in 2001, with 50,000 total patients, and remains incurable despite conventional and high dose therapies. Novel therapeutic interventions are therefore urgently needed with targets unique to the tumor cell and its microenvironment. The major goal of the current proposal, "Host-Tumor Cell Interactions in Myeloma: Therapeutic Applications", is to develop novel therapies targeting host-tumor cell interactions to overcome drug resistance and achieve long-term disease free survival and potential cure of MM. This Program builds upon and extends progress during the prior funding period and now has three major goals. First, we will attempt to therapeutically exploit the interaction of the allogeneic donor immune response against MM and define target antigens for novel therapeutics (Project by Ritz). Second, we will attempt to augment autologous anti-MM immunity using vaccination strategies, and similarly identify novel target antigens (Project by Munshi). In each case molecular identification and validation of novel targets will derive MM specific immune therapies. Importantly, our preclinical in vitro as well as in vivo animal models of MM cells in the BM milieu, demonstrate that novel agents targeting the MM cell-host bone marrow (BM) interaction can overcome classical drug resistance. Our derived clinical trials show that these agents can achieve responses, in some cases complete responses, in the majority of patients with MM refractory to all known current therapies. Therefore a new and important goal of this Program (Project by Anderson) is to define and validate MM-host interactions as targets in a new treatment paradigm for MM. Administrative and Research Nursing (A) and Biostatistics/ Bioinfomatics (B) Cores will assist in design, conduct, analysis, and reporting of laboratory and clinical studies. Immune Assessment Core (C) will provide immunological monitoring after these novel therapies. This Program therefore represents an integrated, interrelated, and interdependent series of three Projects and three Cores which interact on both a scientific and clinical level. It is anticipated, both within and between projects, that laboratory based mechanistic studies will translate to clinical studies, and that conversely, observations from clinical protocols will suggest new basic investigations. Ultimately our goal is to validate MM-host cell interactions as a target for novel therapeutics to improve patient outcome in MM.