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是一种治疗三阴性乳腺癌的免疫疗法：Agilvax正在发展为癌症 采用其专有的病毒样颗粒(VLP)平台技术的免疫疗法和疫苗。Agilvax领先 产品AX09是一种针对肿瘤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 侵袭性，复发率高，与其他类型的乳房相比，总体预后较差 癌症。转移性TNBC患者的平均5年生存率仅为26.1%。TNBC更有可能 发生在40岁以下的女性，非洲裔美国人和西班牙裔美国人的发病率更高 与高加索人的人口相比。据估计，将有30,000名妇女被诊断为 2017年，TNBC。 AX09靶向乳腺癌干细胞预防复发和转移：没有CSC靶向 现有的治疗方法，迫切需要为受影响的患者开发治疗方法。 由TNBC提供。AX09由一个VLP组成，该VLP显示过度表达的蛋白质XCT的特定部分 在乳腺癌干细胞(BCSC)中，并有助于化疗耐药和转移。 AX09在针对TNBC的各种治疗方法的新兴市场中处于有利地位， 将越来越多地通过新的生物标记物和分子靶标来划分患者群体。由于他们的 对放射和化疗的抵抗，BCSC代表了复发和转移进化的储存库 和最初治疗后的进展。AX09产生针对BCSC的寡克隆抗体反应 目标，xct，这将消除BCSC作为复发的来源。 Agilvax的快速通道SBIR目标包括临床前工作、cGMP制造和 毒理学研究：Agilvax这笔赠款的目标是完成其临床前工作，包括上游和 基于AX09下游工艺的开发，该公司在开发过程中成功使用了这些工艺 另一款基于VLP的产品。作为其第一个目标的一部分，Agilvax将通过确定 最佳给药方案，在第二个肿瘤模型中确认疗效，并评估AX09的组合 与其他化疗药物一起规划I期试验设计。Agilvax将继续进行cGMP 生产和验证研究和主细胞库，以完成cGMP的制造和 AX09原料药和制剂的释放试验。根据Agilvax的主要观点的推荐 作为乳腺癌领域的领军人物，一项使用新西兰大白兔进行的单一非临床毒理学研究正在计划中。