Lentiviral Vectors for TCR Immunotherapy Targeted to melanoma

用于针对黑色素瘤的 TCR 免疫治疗的慢病毒载体

• 批准号: 7224655
• 负责人: Boro Dropulic
• 金额: $ 24.3万
• 依托单位: LENTIGEN CORPORATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-28 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7224655
• 关键词: clinical research; immunotherapy; melanoma; neoplasm /cancer

DESCRIPTION (provided by applicant): Project Summary/Abstract: The overall goal of this proposal is to evaluate the novel concept whether using lentiviral-engineered T cells that express high affinity T cell receptor (TCR) capable of recognizing the tyrosinase:368-376 epitope, a melanoma/melanocytes differentiation tumor associated antigen have improved efficacy for melanoma immunotherapy. According to the American Cancer Society melanoma is currently the 6th most common cancer in American men and the 7th most common in American women. In this proposal, we will test the fundamental hypothesis that human T cells with redirected specificity for melanoma can be created by using lentiviral vector technology and can offer a clinically relevant and successful therapeutic approach. The ultimate goal is the development of a novel and improved therapy for melanoma, a type of tumor for which the current therapies do not offer satisfactory results. Lentiviral vectors (LVs) have been successfully evaluated in Phase l clinical trials in patients with HIV/AIDS, offering the possibility to more broadly apply this technology for the treatment of other diseases, particularly cancer. Lentigen's collaborator Dr. Michael Nishimura has helped pioneer adoptive immunotherapy as a potential therapeutic approach for melanoma. Therefore, in Aim 1 of this proposal, we will develop self inactivating (SIN) LVs expressing a and B chains of the TCR capable of recognizing the tyrosinase: 368-376 epitope. In Aim 2, together with Dr. Nishimura's team, we will test safety and efficacy of LV-TCR transduced T cells in preventing melanoma tumor growth and treating established tumors in vivo. We will carry out 2 general types of experiments in order to test the in vivo efficacy and engraftment potential of our lentiviral vectors expressed in engineered human T cells. In summary, Lentigen Corp. and Dr. Nishimura's laboratory are uniquely positioned to provide the first comprehensive evaluation of the redirected T cell approach to generate anti-tumor effects in melanoma patients and to apply this in a future clinical trial for patients with this life threatening malignancy. Project Narrative: The ultimate goal of this proposal is the development of a novel and improved immunotherapy therapy for melanoma, a tumor for which the current therapies do not offer satisfactory results. This therapy is based on activation of immune cells that will be manipulated in the laboratory and put back to patient to fight melanoma tumor cells. Because of its great potential to offer a solution for those patients failing other therapies, this therapy will have significant relevance for cancer patients with melanoma and health care providers in the United States and worldwide.

描述（由申请人提供）：项目摘要/摘要：本提案的总体目标是评估使用表达高亲和力 T 细胞受体（TCR）的慢病毒工程 T 细胞（能够识别酪氨酸酶：368-376 表位，黑色素瘤/黑色素细胞分化肿瘤相关抗原）的新概念是否可以提高黑色素瘤免疫治疗的功效。根据美国癌症协会的数据，黑色素瘤目前是美国男性中第六大常见癌症，美国女性中第七大常见癌症。在本提案中，我们将测试一个基本假设，即可以通过使用慢病毒载体技术创建对黑色素瘤具有重定向特异性的人类 T 细胞，并可以提供临床相关且成功的治疗方法。最终目标是开发一种新型且改进的黑色素瘤疗法，目前的疗法无法提供令人满意的结果。黑色素瘤是一种肿瘤。慢病毒载体（LV）已在艾滋病毒/艾滋病患者的 I 期临床试验中成功进行了评估，为更广泛地应用该技术治疗其他疾病（特别是癌症）提供了可能性。 Lentigen 的合作者 Michael Nishimura 博士帮助开创了过继免疫疗法作为黑色素瘤的潜在治疗方法。因此，在本提案的目标 1 中，我们将开发表达 TCR 的 a 链和 B 链的自失活 (SIN) LV，能够识别酪氨酸酶：368-376 表位。在目标 2 中，我们将与 Nishimura 博士的团队一起测试 LV-TCR 转导 T 细胞在体内预防黑色素瘤生长和治疗已形成肿瘤的安全性和有效性。我们将进行 2 种一般类型的实验，以测试我们的慢病毒载体在工程化人类 T 细胞中表达的体内功效和植入潜力。总之，Lentigen Corp. 和 Nishimura 博士的实验室具有独特的优势，可以对重定向 T 细胞方法在黑色素瘤患者中产生抗肿瘤作用提供首次全面评估，并将其应用于未来针对这种危及生命的恶性肿瘤患者的临床试验。项目叙述：该提案的最终目标是开发一种新型且改进的黑色素瘤免疫疗法，目前的疗法无法提供令人满意的结果。这种疗法基于免疫细胞的激活，这些细胞将在实验室中进行操作，然后放回患者体内以对抗黑色素瘤细胞。由于它具有为其他疗法失败的患者提供解决方案的巨大潜力，因此该疗法将对美国和世界各地的黑色素瘤癌症患者和医疗保健提供者具有重要意义。