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癌症，例如黑色素瘤，淋巴瘤和肺癌，以及诸如肝炎等慢性感染疾病的功效。肝炎的障碍。诱导保护性，治疗性，对癌症的治疗性免疫可产生非常高的疫苗，使得癌症的癌症是癌症的较高的癌症。微环境。创新的Immurx方法利用了两种不同的免疫系统激活剂的辅助活性，CD40激动剂和IFN-（2B或Toll-like受体激动剂（TLR*））的合并辅助活性所产生的新颖和专利的协同影响。 IMMRX的独特方法是，组合疗法在体内激活了适应性和先天免疫系统，而不是刺激效应效应T细胞扩张的方法，这将导致持久和有效的免疫力。此外，与单药产品相比，它为刺激患者的保护性免疫提供了一种更有效的方法。 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表明在鼠模型中，抗原特异性T细胞激活显着增加。鉴于这种对免疫功能的有力影响，我们预计该产品将提供突破性的突破，最终可能会释放出各种癌症和慢性传染病的主动免疫疗法的潜力。 Immurx平台的竞争优势已在实体瘤，血液学癌和传染病的动物测试中得到证明。 Immurx产物的最初治疗靶标是晚期黑色素瘤，这是一种毁灭性的癌症，对免疫调节剂的反应低但可再现的反应。这验证了对这种疾病的Immurx主动疫苗方法的使用。 IFN-（2B作为单一药物被批准用于治疗III期黑色素瘤，但对整体生存具有边缘作用。Immurx的辅助平台和疫苗技术将为临床医生提供对IFN-的显着改善（单一疗法，使单一治疗能够单一治疗以刺激肿瘤特异性效应T细胞的高频，从而增加肿瘤的肿瘤较晚的肿瘤酸酸盐，以增加肿瘤的高频。 要求该SBIR第二阶段奖的资金将用于执行逐步和顺序的交配活动，这将推动这项激动人心的技术介绍诊所及其最终的批准，以用于治疗人类的癌症。 公共卫生相关性：Immurx正在开发一种新颖而强大的免疫治疗产品来刺激免疫系统。这将大大提高现有和新的治疗疫苗治疗癌症，例如黑色素瘤，淋巴瘤和肺癌以及诸如乙型肝炎的慢性传染病。该产品将由一种单一注射组成，该注射将增加两种类型的免疫系统功能，并提供持久和有效的反应。最初的产品将被开发并测试晚期黑色素瘤的功效。该提案要求为开发活动提供资金，这将使Immurx能够将产品转移到最终的人类临床评估中，但不要求用于临床试验的资金。