Preclinical Development of a Novel and Powerful Immunotherapeutic

描述(申请人提供)：ImmuRx正在开发一种新型和有效的免疫治疗产品，以刺激免疫系统。这将大大提高现有和新的治疗性疫苗对黑色素瘤、淋巴瘤和肺癌等癌症以及丙型肝炎等慢性传染病的治疗效果。对癌症抗原诱导保护性、治疗性免疫的障碍一直是无法创造出能够在癌症和患者微环境中诱导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-CD40激动剂和干扰素-(2b)或Toll样受体激动剂(TLR*)的联合佐剂活性所产生的新颖和专利的协同影响。 ImmRx的独特方法是，联合疗法在体内同时激活适应性免疫系统和天然免疫系统，而不是刺激效应性T细胞体外扩张的方法，这将导致持久有效的免疫。此外，与单一制剂产品相比，它提供了一种更有效的手段来刺激患者的保护性免疫。CD40激动剂、TLR激动剂和干扰素都已在临床上分别用于治疗免疫反应性癌症，结果通常令人失望。内含子(R)A(干扰素-(2b)是一种用于治疗晚期/高风险黑色素瘤患者的商业化治疗药物，但该产品的使用充其量是边际生存增加，并以显著的毒性为代价。 在小鼠模型中，ImmuRx已经显示出抗原特异性T细胞激活的显著增加。鉴于这种对免疫功能的强大影响，我们预计该产品将提供一项突破，最终可能释放主动免疫疗法的潜力，用于各种癌症和慢性传染病。ImmuRx平台的竞争优势已在实体肿瘤、血液病和传染病的动物试验中得到证明。ImmuRx产品的初始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很低，但可重复。这验证了ImmuRx对这种疾病的活性疫苗方法的使用。干扰素-(2b)作为单一药物被批准用于治疗III期黑色素瘤，但对总体生存率影响甚微。ImmuRx的佐剂平台和疫苗技术将为临床医生提供比单一疗法更大的改进，使单一疗法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。 为这项SBIR第二阶段奖励申请的资金将用于执行循序渐进的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，并最终被批准用于治疗人类癌症。

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.