A Novel Immunotherapy Targeting Cancer Stem Cells for the Treatment of Triple-Negative Breast Cancer

一种针对癌症干细胞的新型免疫疗法治疗三阴性乳腺癌

• 批准号: 9927778
• 负责人: Joseph Patti
• 金额: $ 84.59万
• 依托单位: AGILVAX, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927778
• 关键词: 4T1; Abraxane; African American; Aftercare; Age; Antibodies; Antibody Response; Biological; Cancer Patient; Cancer Vaccines; Caucasians; Cell physiology; Cells; Chemicals; Clinic; Control Animal; Cyclic GMP; Cystine; Data; Defect; Development; Diagnosis; Disease; Disease Progression; Distal; Dose; Drug resistance; Drug usage; Engineering; Enzyme-Linked Immunosorbent Assay; Equilibrium; Evolution; Excision; Formulation; Glutamates; Glutathione; Goals; Grant; Growth; Guidelines; Hispanics; Human; Immunize; Immunoglobulin G; Immunotherapy; Inbred BALB C Mice; Incidence; Intake; Intramuscular; Knockout Mice; Lead; Measures; Messenger RNA; Metastatic Neoplasm to the Lung; Modeling; Molecular Target; Mus; Neoplasm Metastasis; New Zealand; Normal Cell; Oryctolagus cuniculus; Outcome; Oxidation-Reduction; Pathway interactions; Patients; Pharmaceutical Preparations; Phase I Clinical Trials; Population; Positioning Attribute; Primary Neoplasm; Process; Property; Proteins; Radiation; Recommendation; Recurrence; Regimen; Relapse; Reproducibility; Research; Resistance; Running; Safety; Site; Small Business Innovation Research Grant; Solid Neoplasm; Source; Survival Rate; TAL1 gene; Technology; Technology Transfer; Testing; Therapeutic; Toxic effect; Toxicology; Tumor Stem Cells; Vaccines; Validation; Virus-like particle; Woman; Work; antiporter; base; cGMP production; cancer immunotherapy; cancer stem cell; cancer therapy; capecitabine; cell bank; cell type; chemotherapeutic agent; chemotherapy; combinatorial; design; docetaxel; dosage; flexibility; immunogenic; immunogenicity; inhibiting antibody; malignant breast neoplasm; manufacturing process development; mouse model; neoplastic cell; novel; novel marker; overexpression; patient population; phase 2 study; phase I trial; pre-clinical; preclinical development; preclinical study; prevent; programs; response; self-renewal; stem cell therapy; targeted treatment; therapeutic development; therapeutic target; therapy resistant; trial design; triple-negative invasive breast carcinoma; tumor; tumor growth

Agilvax’s AX09 is an Immunotherapy for Triple-Negative Breast Cancer: Agilvax is developing cancer immunotherapies and vaccines with its proprietary virus-like-particle (VLP) platform technology. Agilvax’s lead product, AX09, is an immunotherapy for triple-negative breast cancer (TNBC) targeting cancer stem cells (CSC) that is designed for use in combination with existing and emerging therapies. TNBC is extremely aggressive with high rates of recurrence and overall poor outcomes as compared to other forms of breast cancer. The average 5-year survival rate for metastatic patients with TNBC is only 26.1%. TNBC is more likely to occur in women under the age of 40, and the rate of incidence is higher in African-American and Hispanic populations as compared to Caucasian populations. It is estimated that 30,000 women will be diagnosed with TNBC in 2017. AX09 Targets Breast Cancer Stem Cells to Prevent Relapse and Metastasis: With no CSC targeted therapies currently available, there is a critical need for the development of therapeutics for patients impacted by TNBC. AX09 is composed of a VLP that displays a specific portion of a protein, xCT, that is overexpressed in breast cancer stem cells (BCSC) and contributes to chemotherapeutic drug resistance and metastasis. AX09 is favorably positioned in the emerging market of various treatment approaches targeting TNBC, which will increasingly segment the patient population by novel biomarkers and molecular targets. Due to their resistance to radiation and chemotherapies, BCSC represent a reservoir for the relapse, metastatic evolution and progression after initial treatment. AX09 produces an oligoclonal antibody response against the BCSC target, xCT, that will eliminate BCSC as a source of recurrence. Agilvax’s Aims for the Fast-Track SBIR Include Preclinical Work, cGMP Manufacturing and a Toxicology Study: Agilvax’s goals for this grant are to complete its preclinical work, including upstream and downstream process development of AX09 based on processes the company successfully used in developing another VLP-based product. As part of its first goal, Agilvax will strengthen AX09 efficacy by determining the optimal dosage regimen, confirming efficacy in a second tumor model, and assess the combination of AX09 with other chemotherapeutic agents in planning for the Phase I trial design. Agilvax will proceed with cGMP production and validation of research and master cell banks in order to complete cGMP manufacturing and release testing of AX09 drug substance and drug product. Upon the recommendation of Agilvax’s Key Opinion Leaders in breast cancer, a single nonclinical toxicology study using New Zealand white rabbits is planned.

Agilvax的AX09是三阴性乳腺癌的免疫疗法：Agilvax正在发展癌症 免疫疗法和疫苗及其专有病毒样粒子（VLP）平台技术。阿吉瓦克斯的领导 产品AX09是针对癌症干细胞的三阴性乳腺癌（TNBC）的免疫疗法 （CSC）旨在与现有和新兴疗法结合使用。 TNBC非常 与其他形式的乳房相比 癌症。 TNBC转移性患者的平均5年生存率仅为26.1％。 TNBC更有可能 在40岁以下的妇女中发生，非裔美国人和西班牙裔的事件发生率较高 与高加索人群相比，种群。据估计，将有30,000名妇女被诊断出患有 TNBC在2017年。 AX09靶向乳腺癌干细胞以防止复发和转移：没有CSC的目标 目前可用的疗法，对受影响的患者开发治疗剂至关重要 由TNBC。 AX09由显示出过表达的蛋白质的特定部分的VLP组成 在乳腺癌干细胞（BCSC）中，有助于化学治疗耐药性和转移。 AX09在针对TNBC的各种治疗方法的新兴市场中有利地定位于此， 将通过新型的生物标志物和分子靶标增加患者人群的细分。由于他们 BCSC对辐射和化学疗法的耐药性代表了救济，转移性进化的储层 和初始治疗后的进展。 AX09对BCSC产生寡克隆抗体反应 目标，XCT，将消除BCSC作为复发的来源。 阿吉瓦克斯（Agilvax 毒理学研究：Agilvax的这笔赠款目标是完成其临床前工作，包括上游和 基于公司成功用于开发的公司，AX09的下游过程开发 另一个基于VLP的产品。作为其第一个目标的一部分，Agilvax将通过确定 最佳剂量方案，确认第二个肿瘤模型的效率，并评估AX09的组合 与其他化学治疗剂计划I期试验设计。 Agilvax将继续使用CGMP 为了完成CGMP制造和 AX09药物和药物产品的释放测试。根据阿吉尔瓦克斯的关键意见的建议 乳腺癌的领导者计划使用新西兰白兔子进行一项非临床毒理学研究。