Preclinical Development of a Novel and Powerful Immunotherapeutic

新型强效免疫治疗药物的临床前开发

• 批准号: 8213450
• 负责人: Susan Dana Jones
• 金额: $ 84.76万
• 依托单位: IMMURX LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-20 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8213450
• 关键词: Active Immunotherapy; Adjuvant; Advanced Development; Aftercare; Agonist; Animal Testing; Antibodies; Antigens; Award; B Cell Proliferation; Biological Assay; Blood specimen; CD8B1 gene; Cancer Patient; Cell Line; Cell surface; Cellular Immunity; Chinese Hamster Ovary Cell; Chronic; Clinic; Clinical; Clinical Treatment; Clinical Trials; Combined Modality Therapy; Communicable Diseases; Data; Development; Disease; Dose; Endotoxins; Engineering; Enzyme-Linked Immunosorbent Assay; Frequencies; Funding; Goals; Growth; Health; Hematologic Neoplasms; Hepatitis C; Hepatotoxicity; Human; Immune; Immune response; Immune system; Immunity; Immunotherapeutic agent; In Vitro; Injection of therapeutic agent; Interferon-alpha; Interferons; Interleukin-12; Introns; Legal patent; Lymphoma; Macaca fascicularis; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Modeling; Monitor; Mus; Organ; Patients; Phase; Primates; Production; Productivity; Regimen; Request for Proposals; Serum; Small Business Innovation Research Grant; Solid Neoplasm; Staging; T cell response; T-Cell Activation; T-Lymphocyte; TNFRSF5 gene; Target Populations; Technology; Therapeutic; Therapeutic Uses; Toll-like receptors; Toxic effect; Toxicology; Transgenic Mice; Treatment Efficacy; Tumor Antigens; Vaccines; Viral; analytical method; base; cancer therapy; cost; cytokine; design; dosage; efficacy testing; expression vector; flasks; high risk; human monoclonal antibodies; immune function; in vivo; innovation; liver function; manufacturing process; melanoma; mouse model; nonhuman primate; novel; novel therapeutics; novel vaccines; pre-clinical; preclinical study; research clinical testing; response; therapeutic target; therapeutic vaccine; tumor

DESCRIPTION (provided by applicant): ImmuRx is developing a novel and potent immunotherapeutic product to stimulate the immune system. This will significantly increase the efficacy of existing and new therapeutic vaccines for the treatment of cancers such as melanoma, lymphoma and lung cancer and for chronic infectious diseases such as Hepatitis C. The barrier to the induction of protective, therapeutic immunity to cancer antigens has been the inability to create vaccines that can elicit very high numbers of tumor-reactive T cells in the cancer and patient microenvironment. The innovative ImmuRx approach takes advantage of the novel and patented synergistic impact resulting from the combined adjuvant activity of two different immune system activators, a CD40 agonist and IFN-(2b or a Toll-like receptor agonist (TLR*). ImmRx's unique approach is that the combination therapy activates both the adaptive and innate immune system in vivo, as opposed to the approach of stimulating effector T cell expansion ex vivo, and this will leads to a long lasting and effective immunity. Further, it provides a much more effective means of stimulating protective immunity in patients compared to single agent products. CD40 agonists, TLR agonists, and IFN( have all been tried separately in the clinic for treatment of immune-responsive cancers and the results have generally been disappointing. INtron(r) A (IFN-(2b) is a commercially available therapeutic used to treat patients with advanced/high-risk melanoma, but use of this product has resulted in marginal survival gains at best and at a cost of significant toxicity. ImmuRx has demonstrated a significant increase in antigen-specific T cell activation in murine models. Given this potent impact on immune function, we expect this product will provide a breakthrough that may finally unlock the potential of active immunotherapy for a wide variety of cancers and chronic infectious disease. The competitive advantage of the ImmuRx platform has been demonstrated in animal testing in solid tumors, hematologic cancers and infectious disease. The initial therapeutic target for ImmuRx's product is advanced melanoma, a devastating cancer that has a low but reproducible response to immunomodulatory agents. This validates the use of ImmuRx's active vaccine approach for this disease. IFN-(2b as a single agent is approved for treatment of Stage III melanoma, but has marginal effect on the overall survival. ImmuRx's adjuvant platform and vaccine technology will provide clinicians with a significant improvement over IFN-( monotherapy, enabling a single treatment to stimulate high frequencies of tumor-specific effector T cells and to increase tumor regression in late stage melanoma. The funding requested for this SBIR Phase II award will be used to perform step-wise and sequential IND-enabling activities that will propel this exciting technology towards the clinic and its eventual approval for use in the treatment of cancers in humans. PUBLIC HEALTH RELEVANCE: ImmuRx is developing a novel and powerful immunotherapeutic product to stimulate the immune system. This will significantly increase the efficacy of existing and new therapeutic vaccines for treatment of cancers such as melanoma, lymphoma and lung cancer and for chronic infectious diseases such as Hepatitis C. The product will consist of a single injection that will increase both types of immune system function and will provide a long lasting and effective response. The initial product will be developed and tested for efficacy in advanced melanoma. This proposal requests funding for development activities that will enable ImmuRx to move the product towards eventual human clinical evaluation but does not request funding for clinical trials.

描述（由申请人提供）：ImmuRx 正在开发一种新颖且有效的免疫治疗产品来刺激免疫系统。这将显着提高现有和新的治疗性疫苗治疗黑色素瘤、淋巴瘤和肺癌等癌症以及丙型肝炎等慢性传染病的功效。诱导针对癌症抗原的保护性、治疗性免疫的障碍已被克服。无法研制出能够在癌症和患者微环境中引发大量肿瘤反应性 T 细胞的疫苗。创新的 ImmuRx 方法利用了两种不同免疫系统激活剂（CD40 激动剂和 IFN-(2b 或 Toll 样受体激动剂 (TLR*)）的联合佐剂活性所产生的新型专利协同效应。 ImmRx的独特方法是，联合疗法在体内激活适应性和先天免疫系统，而不是在体外刺激效应T细胞扩增，这将带来持久且有效的免疫。此外，与单剂产品相比，它提供了一种更有效的刺激患者保护性免疫力的方法。 CD40 激动剂、TLR 激动剂和 IFN（均已在临床上分别尝试用于治疗免疫反应性癌症，但结果通常令人失望。INtron(r) A (IFN-(2b) 是一种市售治疗剂，用于治疗免疫反应性癌症）治疗晚期/高危黑色素瘤患者，但使用该产品充其量只能带来边际生存增益，并以显着毒性为代价。 ImmuRx 已证明小鼠模型中抗原特异性 T 细胞活化显着增加。鉴于对免疫功能的这种强大影响，我们预计该产品将提供突破，最终可能释放主动免疫疗法治疗多种癌症和慢性传染病的潜力。 ImmuRx平台的竞争优势已在实体瘤、血液癌症和传染病的动物试验中得到证明。 ImmuRx 产品的最初治疗目标是晚期黑色素瘤，这是一种毁灭性的癌症，对免疫调节剂的反应较低，但可重复。这验证了 ImmuRx 的主动疫苗方法对于这种疾病的使用。 IFN-(2b 作为单药被批准用于治疗 III 期黑色素瘤，但对总生存期影响有限。ImmuRx 的辅助平台和疫苗技术将为临床医生提供较 IFN-( 单药治疗显着改善，使单次治疗能够刺激高频率的肿瘤特异性效应 T 细胞并促进晚期黑色素瘤的肿瘤消退。 SBIR II 期奖项申请的资金将用于执行分步、连续的 IND 支持活动，这将推动这项令人兴奋的技术走向临床并最终批准用于治疗人类癌症。 公共健康相关性：ImmuRx 正在开发一种新颖且强大的免疫治疗产品来刺激免疫系统。这将显着提高现有和新型治疗疫苗的功效，用于治疗黑色素瘤、淋巴瘤和肺癌等癌症以及丙型肝炎等慢性传染病。该产品将由单次注射组成，可增强两种类型的免疫系统功能并将提供持久且有效的响应。最初的产品将被开发并测试其对晚期黑色素瘤的疗效。该提案要求为开发活动提供资金，使 ImmuRx 能够将产品推向最终的人体临床评估，但不要求为临床试验提供资金。