A low-cost topical immunotherapy formulation suitable for treating cervical cancer in low and middle income countries and low-resource settings in the U.S.

该项目的目标是提供一种负担得起的免疫疗法来治疗中晚期宫颈癌。 和美国的中等收入国家(LMIC)和低资源环境。一个更长期的目标是尽早治疗 对宫颈异型增生的分期进行评估，并评估对病原体人乳头瘤病毒(HPV)的免疫力。这个 宫颈癌的沉重负担和死亡不成比例地落在了资源贫乏的妇女身上 设置。克服治疗障碍，即缺乏基础设施、训练有素的专家、专门设备、 冷链和财政资源需要能够实现的治疗方法的范式转变 由这里提出的创新免疫治疗剂。 IFX-Hu2.1(SN63/016,700)是一种以乳膏为基础的治疗性免疫调节剂，将针对稳定性和 性能。我们的IFX-HU2家族含有一种质粒DNA(PDNA)原料药，可以生产 只需目前免疫疗法费用的一小部分。PDNA编码一种复杂的细菌抗原Emm55。 当Emm55表达在肿瘤细胞表面时，它会吸引抗原提呈细胞和其他固有的细胞 免疫反应。非自身表位，如肿瘤和HPV抗原，然后以这样的方式暴露，以设置 上调多种抗原性细胞和体液适应性免疫反应。基于Emm55的疗法诱导 个性化、多价、系统和持续的免疫反应，并有可能治疗 通过增强肿瘤识别、免疫激活和表位扩散，扩大癌症的范围。 在多项动物研究中，瘤内注射IFX-Hu2.0具有既定的安全性，目前 正在进行皮肤黑色素瘤、默克尔细胞癌和皮肤的第一阶段人体临床试验 鳞状细胞癌。我们的初步临床数据证实了临床前的观察结果，表明 激活T、B细胞免疫反应，减少肿瘤，无短期或长期不良反应。 我们建议使用现有的方法和方法来优化IFX-Hu2.1配方的温度稳定性 模特们。体外评价，包括标准质量控制方法和人阴道上皮 肿瘤模型，随后将在小鼠体内进行摄取、表达和疾病进展的研究 宫颈癌模型。室温储存和自我管理将避免繁琐的诊所就诊， 改善预后，保持生育能力。IFX-Hu2.1乳膏配方将提供无毒癌症 治疗需要最低限度的支持性护理，具有独特的交付方式，并且 对服务不足人群的适用性/影响。通过完成这些研究获得的数据将使 形态发生公司将提交一份研究性新药申请，以进行一项针对女性的临床试验 当地社区医院(低资源环境)和南非(LMIC)。这些试验将是 SBIR第二阶段提案。

The goal of this project is to deliver an affordable immunotherapy to treat advanced cervical cancer in low- and middle-income countries (LMICs) and low-resource settings in the U.S. A longer-term goal is to treat earlier stages of cervical dysplasia and assess immunity to the causative agent, human papillomavirus (HPV). The heavy burden of suffering and death from cervical cancer disproportionately falls on women in resource poor settings. Overcoming barriers to treatment, i.e. lack of infrastructure, trained specialists, specialized equipment, cold chain, and financial resources, requires a paradigm shift in the approach to treatment that can be achieved by the innovative immunotherapeutic agent proposed here. IFx-Hu2.1 (SN63/016,700) is a cream-based therapeutic immunomodulator that will be optimized for stability and performance. Our IFx-Hu2 family contains a plasmid DNA (pDNA) bulk drug substance, which can be produced for a fraction of the cost of current immunotherapies. The pDNA encodes a complex bacterial antigen, Emm55. When expressed on the tumor cell surface, Emm55 attracts antigen presenting cells and other cells of the innate immune response. Non-self-epitopes such as tumor and HPV antigens are then exposed in such a way as to set up multi-antigenic cellular and humoral adaptive immune responses. Emm55-based therapies induce personalized, multivalent, systemic, and sustained immune responses and have the potential to treat a broad range of cancers through enhanced tumor recognition, immune activation and epitope spreading. Intralesional injection of IFx-Hu2.0 has an established safety profile in multiple animal studies and is currently being tested in Phase 1 human clinical trials for cutaneous melanoma, Merkel cell carcinoma and cutaneous squamous cell carcinoma. Our preliminary clinical data corroborate pre-clinical observations, showing the activation of T- and B-cell immune responses and tumor reduction, with no short or long-term adverse effects. We propose to optimize the IFx-Hu2.1 formulation for temperature stability using established methods and models. In vitro evaluation, to include standard quality control methods and a human vaginal epithelium carcinoma model, will be followed by in vivo uptake, expression, and disease progression studies in a mouse model of cervical cancer. Room temperature storage and self-administration will circumvent onerous clinic visits, improve prognosis and preserve fertility. IFx-Hu2.1 cream formulation will provide a non-toxic cancer therapeutic treatment with minimal supportive care requirements, featuring unique delivery, and high applicability/impact to underserved populations. The data obtained by completing these studies will position Morphogenesis, Inc. to submit an Investigational New Drug application to conduct a clinical trial for women in a local community hospital (low-resource setting) and in South Africa (LMIC). These trials will be the objective of an SBIR Phase 2 proposal.