Gordon Neal F, Clark Brian L
Antigenics Inc., Lexington, MA 02421, USA.
Methods. 2004 Jan;32(1):63-9. doi: 10.1016/s1046-2023(03)00188-9.
Based on genetic diversity in the population, there is an expectation, born out by decades of experience, that a given drug or treatment will not be equally efficacious for all patients. While this fact cannot be avoided, with ever increasing knowledge of the drug's biological mechanism of action and the relationship between efficacy and the patient's genetic profile, more directed treatments, with greater potential for efficacy are becoming possible. For example, Herceptin, Genentech's antibody based treatment for HER2 positive metastatic breast cancer, is prescribed based on the results of a diagnostic test, the outcome of which is able to screen out patients who have no chance of responding to the treatment. At the extreme of tailoring medicines to those patients who will receive the greatest benefit, is an autologous, or patient specific approach. Oncophage, a cancer vaccine in late stage clinical trials, is designed to accommodate the unique genetic mutations underlying each patient's cancer. This chapter of the book presents the challenges involved in bringing autologous HSP-based vaccines to commercial reality based on the experiences gained to date in the clinical manufacture of Oncophage. Two guiding principles have dominated our efforts. First, only the product should be autologous. All processes should be standardized to the greatest extent possible. Second, maintaining complete segregation between patient samples at all steps of processing is paramount.
基于人群中的基因多样性，数十年的经验表明，某种特定药物或治疗方法对所有患者的疗效并非完全相同。虽然这一事实无法避免，但随着对药物生物学作用机制以及疗效与患者基因谱之间关系的了解不断增加，更具针对性、疗效潜力更大的治疗方法正变得可行。例如，基因泰克公司生产的用于治疗HER2阳性转移性乳腺癌的抗体药物赫赛汀，是根据诊断测试结果来开处方的，该测试结果能够筛选出对治疗无反应可能性的患者。将药物精准定制给受益最大的患者的极致做法是采用自体或针对患者个体的方法。Oncophage是一种处于后期临床试验阶段的癌症疫苗，旨在适应每位患者癌症所特有的基因突变。本书的这一章基于到目前为止在Oncophage临床生产中获得的经验，介绍了将基于自体热休克蛋白的疫苗推向商业现实所涉及的挑战。有两条指导原则主导着我们的工作。第一，只有产品应该是自体的。所有流程应尽可能标准化。第二，在处理的所有步骤中，保持患者样本的完全隔离至关重要。
