Novel Biologic Therapies for Hodgkin's Lymphoma

霍奇金淋巴瘤的新型生物疗法

• 批准号: 7805614
• 负责人: YVETTE L. KASAMON
• 金额: $ 14.09万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-05 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7805614
• 关键词: Address; Affect; Allogenic; Antibody Therapy; B-Lymphocytes; Biological Assay; Biological Markers; Biological Response Modifier Therapy; Cancer Vaccines; Cells; Clinical; Clinical Research; Clinical Trials; Cyclophosphamide; DNA; DNA Markers; Disease; Dose; Effectiveness; Evaluation; Goals; Hodgkin Disease; Human Herpesvirus 4; Immune; Immunologics; Immunotherapeutic agent; Immunotherapy; In Vitro; Investigation; Laboratories; Lymphoma; MS4A1 gene; Malignant Neoplasms; Modeling; Monitor; NOD/SCID mouse; Newly Diagnosed; Outcome; Patients; Pilot Projects; Plasma; Population; Reed-Sternberg Cells; Relapse; Reporter; Risk; Role; Stem cells; System; Testing; Thinking; Time; Transplantation; Vaccines; base; cancer stem cell; improved; insight; new therapeutic target; novel; response; rituximab; self-renewal; stem cell population; stem cell therapy; translational study; tumor; tumor growth

DESCRIPTION (provided by applicant): PROJECT SUMMARY: Recent insights into the B-cell origin of the Reed-Sternberg (RS) cell point to new immunotherapeutic targets for classical HL (cHL). It has been appreciated that many cancers are comprised of cells that may be functionally divided into two groups: 1) relatively differentiated cells that form the bulk of the tumor, and 2) cells that may be quite distinct phenotypically but retain the capacity to self- renew. In vitro studies by our group suggest a role for rituximab in cHL as a potential cancer stem cell targeting agent. The first clinical trial integrates vaccine and antibody therapies for relapsed cHL, exploring the cancer stem cell concept as well as the possible role for tumor vaccines for cHL following high dose therapy. The second trial expands upon the concept of cancer stem cell targeting in newly diagnosed cHL patients and explores DNA markers for assessing the clinical impact of stem cell therapies. The long-term overall objective is to investigate novel immunotherapies for cHL based on the concept of cancer stem cell targeting, and the hypothesis that the HL cancer stem cell is biologically and phenotypically distinct from the RS cell and expresses CD20. Specific Aim 1: Conduct a pilot study of rituximab, high dose cyclophosphamide, and an allogenic tumor vaccine for relapsed cHL; determine whether cellular responses to a tumor vaccine can be generated after high dose therapy and rituximab; and evaluate whether an EBV reporter system is useful in monitoring these responses. Specific Aim 2. Conduct a multicenter clinical trial of rituximab-ABVD for newly diagnosed cHL, and investigate DNA biomarkers for assessing the effectiveness of stem cell targeting agents.

描述（由申请人提供）：项目摘要：对Reed-Sternberg（RS）细胞的B细胞起源的最新见解指向古典HL（CHL）的新免疫治疗靶标。人们认为，许多癌症由可能在功能上分为两组的细胞组成：1）相对分化的细胞形成大部分肿瘤的细胞，以及2）可能在表型上完全不同但保留自我更新的能力。我们小组的体外研究表明，利妥昔单抗在CHL中的作用是潜在的癌细胞靶向剂。第一个临床试验将复发性CHL的疫苗和抗体疗法整合在一起，探索癌症干细胞概念以及高剂量治疗后CHL的肿瘤疫苗的可能作用。第二项试验扩展了新诊断的CHL患者的癌细胞靶向概念，并探索了评估干细胞疗法临床影响的DNA标记。长期的总体目标是根据癌症干细胞靶向的概念研究CHL的新型免疫疗法，以及HL癌干细胞在生物学和表型上与RS细胞不同并表达CD20的假设。具体目标1：进行利妥昔单抗，高剂量环磷酰胺和同种异体肿瘤疫苗的试验研究；确定在高剂量治疗和利妥昔单抗后是否可以产生对肿瘤疫苗的细胞反应；并评估EBV报道系统是否有助于监视这些响应。具体目的2。对新诊断的CHL进行利妥昔单抗ABVD的多中心临床试验，并研究DNA生物标志物以评估干细胞靶向剂的有效性。