A Program of Immune-Based Treatments for Cancer

描述（由申请人提供）：本提案的目标是在新型免疫学临床试验主要研究者计划的框架内为初级临床研究者提供指导。 一些最令人兴奋的新抗癌疗法是基于免疫学的发现。 例如，重组细胞因子和单克隆抗体现在常规用于晚期疾病的治疗，通常与细胞毒性化疗联合使用。 不幸的是，这些方案可能是有毒的，目前还不清楚，这些药物与标准化疗药物的组合是最合乎逻辑的方法，他们的发展。 卡森博士采用的另一种方法是使用细胞因子佐剂来提高免疫疗法的功效。 卡森博士的临床项目集中在两个特定的研究领域：（1）使用白细胞介素-12和其他细胞因子来增强肿瘤对干扰素-α作用的敏感性;和（2）。使用细胞因子增强对抗HER 2/neu单克隆抗体的免疫应答。 这些试验都是从卡森博士的研究实验室的基本实验观察发展而来的。 为了评价这些治疗对患者免疫系统活性和患者肿瘤生长的影响，卡森博士利用患者组织进行了一系列新的相关研究。 这些实验室研究允许对免疫方案进行合理评价，并指导了后续试验的开展。 俄亥俄州州立大学综合癌症中心的一些内科和外科肿瘤学研究员参与了卡森博士临床试验的开发和实施。 他能够在临床研究的许多方面培训这些年轻的研究人员，因为他们评估和治疗参加他的免疫学研究的患者。 在目前的提案中，卡森博士概述了一个以病人为导向的研究的详细计划。 他还为参与这些临床试验的年轻研究人员制定了系统的培训计划，以便他们最终能够生成和管理自己设计的方案。 除了他们的临床研究，学员将从事一系列的教育经验和专业培训课程。 学员还将参加一系列肿瘤学教学会议，并将定期与卡森博士会面，讨论他们的病人和他们的教育经验。 通过CALGB合作小组进行多机构试验的承诺确保了学员将在临床研究的这方面获得宝贵的经验。 最后，特别强调了有关以病人为导向的研究的道德行为的指导。

DESCRIPTION (provided by applicant): The goal of this proposal is to provide mentoring for beginning clinical investigators within the framework of the principal I investigator's program of novel immunotherapeutic clinical trials. Some of the most exciting new anti-cancer therapies are based on immunologic discoveries. For example, recombinant cytokines and monoclonal antibodies are now routinely used in the setting of advanced disease, usually in combination with cytotoxic chemotherapy. Unfortunately, these regimens can be toxic, and it is not clear that combining these agents with standard chemotherapeutic drugs represents the most logical approach to their development. An alternate approach that has been employed by Dr. Carson, is the use of cytokine adjuvants to improve the efficacy of immunologic therapies. Dr. Carson's clinical program has focused on two specific areas of investigation: (1) The use of interleukin-12 and other cytokines to enhance the sensitivity of tumors to the actions of interferon-alpha; and (2). The use of cytokines to augment the immune response to an anti-HER2/neu monoclonal antibody. These trials all have evolved from basic experimental observations that were made in Dr. Carson's research laboratory. In order to, evaluate the effects of these treatments on the activity of the patient's immune system and the growth of the patient's tumor, Dr. Carson has conducted a series of novel correlative studies utilizing patient tissues. These laboratory studies have permitted a rational evaluation of the immunotherapeutic regimens and have guided the development of subsequent trials. A number of Medical and Surgical Oncology Fellows at the Ohio State University Comprehensive Cancer Center have I participated in the development and conduct of Dr. Carson's clinical trials. He has been able to train these young investigators I in many aspects of clinical research as they evaluate and treat patients enrolled in his immunotherapeutic studies. In the current proposal, Dr. Carson has outlined a detailed plan of patient-oriented research. He has also developed a systematic training program for young investigators who are involved in these clinical trials so that they will eventually be able to generate and administer protocols of their own design. In addition to their clinical research, trainees will engage in a series of educational experiences and specialized training sessions. Trainees will also attend a series of oncologic didactic sessions and will meet regularly with Dr. Carson to discuss their patients and their educational experiences. The promise of multi-institutional trials through the CALGB cooperative group insures that trainees will gain valuable experience in this aspect of clinical research. I Finally, a special emphasis has been placed on instruction relating to the ethical conduct of patient-oriented research.