A Program of Immune-Based Treatments for Cancer

描述（由申请人提供）：本提案的目标是在主要研究者的新型免疫治疗临床试验项目框架内为初级临床研究者提供指导。一些最令人兴奋的抗癌新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，通常与细胞毒性化疗联合使用。不幸的是，这些治疗方案可能是有毒的，目前尚不清楚将这些药物与标准化疗药物联合使用是否代表了它们发展的最合乎逻辑的方法。Carson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疗效。Carson博士的临床项目主要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)。利用细胞因子增强抗her2 /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所做的基本实验观察发展而来的。为了评估这些治疗对患者免疫系统活动和患者肿瘤生长的影响，Carson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治疗方案进行合理评估，并指导后续试验的发展。俄亥俄州立大学综合癌症中心的许多内科和外科肿瘤研究员参与了Carson博士临床试验的开发和实施。他已经能够在临床研究的许多方面培训这些年轻的研究者，因为他们评估和治疗参加他的免疫治疗研究的患者。在目前的提案中，卡森博士概述了以患者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一个系统的培训计划，以便他们最终能够制定和管理自己设计的方案。除了临床研究外，受训者还将参加一系列的教育经历和专业培训课程。受训者还将参加一系列肿瘤学教学课程，并定期与卡森医生会面，讨论他们的病人和他们的教育经历。通过CALGB合作小组进行多机构试验的承诺确保受训人员将在这方面的临床研究中获得宝贵的经验。最后，特别强调的是与以患者为导向的研究的伦理行为有关的指导。

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.