Preclinical Development of a Novel and Powerful Immunotherapeutic

描述（由申请人提供）：ImmuRx正在开发一种新型强效免疫抑制剂产品，以刺激免疫系统。这将显著提高现有的和新的治疗性疫苗的功效，用于治疗癌症，如黑色素瘤、淋巴瘤和肺癌，以及慢性传染病，如丙型肝炎。诱导对癌症抗原的保护性、治疗性免疫的障碍一直是无法创造出可以在癌症和患者微环境中引发非常高数量的肿瘤反应性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（CD 40激动剂和IFN-β 2 b或Toll样受体激动剂（TLR*））的联合佐剂活性产生的新型专利协同作用。 ImmRx的独特方法是联合治疗在体内激活适应性和先天性免疫系统，而不是刺激效应T细胞体外扩增的方法，这将导致持久和有效的免疫。此外，与单药产品相比，它提供了一种更有效的刺激患者保护性免疫的方法。CD 40激动剂、TLR激动剂和IFN α都已在临床上分别尝试用于治疗免疫应答性癌症，结果通常令人失望。INtron（r）A（IFN-（2b））是一种用于治疗晚期/高危黑色素瘤患者的市售治疗剂，但使用该产品最多只能获得边际生存率，并以显著毒性为代价。 ImmuRx已证明在鼠模型中抗原特异性T细胞活化显著增加。鉴于这种对免疫功能的强大影响，我们预计这种产品将提供一个突破，最终可能会释放出各种癌症和慢性感染性疾病的主动免疫疗法的潜力。ImmuRx平台的竞争优势已在实体瘤、血液癌症和传染病的动物试验中得到证实。ImmuRx产品的最初治疗目标是晚期黑色素瘤，这是一种对免疫调节剂的反应较低但可重现的毁灭性癌症。这验证了ImmuRx的主动疫苗方法对这种疾病的使用。IFN-β 2b作为单药被批准用于治疗III期黑色素瘤，但对总生存率的影响很小。ImmuRx的佐剂平台和疫苗技术将为临床医生提供比IFN-α单药治疗显著的改善，使单一治疗能够刺激高频率的肿瘤特异性效应T细胞，并增加晚期黑色素瘤的肿瘤消退。 该SBIR第二阶段奖励所需的资金将用于执行逐步和连续的IND使能活动，这些活动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。 公共卫生相关性：ImmuRx正在开发一种新的强大的免疫产品，以刺激免疫系统。这将显著提高现有的和新的治疗性疫苗的功效，用于治疗癌症，如黑色素瘤、淋巴瘤和肺癌，以及慢性传染病，如丙型肝炎。该产品将包括一个单一的注射，将增加两种类型的免疫系统功能，并将提供一个持久和有效的反应。最初的产品将被开发和测试在晚期黑色素瘤中的疗效。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价，但不要求为临床试验提供资金。

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.