Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ

原位产生患者特异性抗原的生物材料癌症疫苗

基本信息

  • 批准号:
    10053676
  • 负责人:
  • 金额:
    $ 42.59万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-12-01 至 2022-11-30
  • 项目状态:
    已结题

项目摘要

Cancer immunotherapies that exploit ex vivo manipulation of a patient's own cells can generate significant anti- tumor immune responses, but present significant practical limitations. Nanoparticle-based antigen presenting systems provide an alternative approach to generate anti-tumor responses without ex vivo cell manipulation, but the defined antigens will likely need to be personalized to each patient. We have demonstrated a new concept, the use of implantable biomaterials that can localize large numbers of dendritic cells (DCs) from the host, and efficiently activate these cells while loading with antigens derived from a tumor biopsy. This approach demonstrated unprecedented ability to promote regression of established tumors in several pre- clinical models, and we have recently initiated a Phase I trial of this new approach to treat stage IV melanoma patients. However, the antigen in this vaccine is derived from a biopsy, leading to the requirement that each vaccine be manufactured for a specific patient, and the vaccine requires surgical implantation. This project is based on the premise that combining delivery of traditional chemotherapeutic agents and biomaterial- based vaccination will lead to therapeutic immune responses, by generating patient-specific antigen in situ, obviating the need to identify or load antigen onto vaccines prior to placement in the body. Our hypothesis will be tested using the following Aims: (1) Develop cryogels capable of being injected intra and/or peritumorally that recruit DCs through GM-CSF release, and control the timing of release of nanoparticles (NPs) containing toll like receptor ligands from the biomaterial vaccine in order to concentrate and activate DCs within the tumor, and enhance their trafficking to the draining lymph node. (2) Determine the impact of an approach to localize immunostimulatory chemotherapeutic agents to tumors on cancer cell death, and determine the impact of combined chemotherapy and vaccination on tumor growth and the tumor-specific host immune response. (3) Examine the ability of vaccination at the primary tumor to yield therapeutic effects on distant tumors in the body, and combine the biomaterial-based vaccine strategy with checkpoint blockade therapy. These studies will utilize both transplantable tumor models and a transgenic melanoma model. This project will result in the development of a new, patient-specific vaccination strategy that does not require personalized manufacturing. We expect this vaccine strategy will synergize with checkpoint blockade therapy, yielding robust and systemic therapeutic benefit.
癌症免疫疗法利用患者自身细胞的离体操作,可以产生显著的抗

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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David J Mooney其他文献

Subcutaneous biodegradable scaffolds for restimulating the antitumour activity of pre-administered CAR-T cells.
皮下可生物降解支架,用于重新刺激预施用的 CAR-T 细胞的抗肿瘤活性。
  • DOI:
    10.1038/s41551-024-01216-4
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    28.1
  • 作者:
    David K. Y. Zhang;Joshua M. Brockman;Kwasi Adu;Yutong Liu;Yoav Binenbaum;Irene de Lázaro;Miguel C. Sobral;Rea Tresa;David J Mooney
  • 通讯作者:
    David J Mooney
Angioid streaks in beta thalassaemia minor.
轻微β地中海贫血出现血管样条纹。
805-4 Biodegradable scaffolds incorporating vascular endothelial growth factor as a novel sustained delivery platform to induce angiogenesis
  • DOI:
    10.1016/s0735-1097(04)92001-3
  • 发表时间:
    2004-03-03
  • 期刊:
  • 影响因子:
  • 作者:
    Qinghua Sun;Ruth Chen;David J Mooney;Sanjay Rajagopalan;P.Michael Grossman
  • 通讯作者:
    P.Michael Grossman

David J Mooney的其他文献

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{{ truncateString('David J Mooney', 18)}}的其他基金

Viscoelasticity and T Cell Production
粘弹性和 T 细胞生产
  • 批准号:
    10566883
  • 财政年份:
    2022
  • 资助金额:
    $ 42.59万
  • 项目类别:
Engineering Skeletal Muscle WIth Biodegradable Hydrogels
用可生物降解水凝胶工程骨骼肌
  • 批准号:
    9894440
  • 财政年份:
    2019
  • 资助金额:
    $ 42.59万
  • 项目类别:
Scaffolds mimicking antigen presenting cells
模拟抗原呈递细胞的支架
  • 批准号:
    9789238
  • 财政年份:
    2018
  • 资助金额:
    $ 42.59万
  • 项目类别:
Scaffolds mimicking antigen presenting cells
模拟抗原呈递细胞的支架
  • 批准号:
    10001355
  • 财政年份:
    2018
  • 资助金额:
    $ 42.59万
  • 项目类别:
Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ
原位产生患者特异性抗原的生物材料癌症疫苗
  • 批准号:
    10305629
  • 财政年份:
    2017
  • 资助金额:
    $ 42.59万
  • 项目类别:
MSC Encapsulation with Thin Gel Coating
具有薄凝胶涂层的 MSC 封装
  • 批准号:
    9383973
  • 财政年份:
    2017
  • 资助金额:
    $ 42.59万
  • 项目类别:
Biomaterial based breast cancer vaccine
基于生物材料的乳腺癌疫苗
  • 批准号:
    8830976
  • 财政年份:
    2013
  • 资助金额:
    $ 42.59万
  • 项目类别:
Biomaterial based breast cancer vaccine
基于生物材料的乳腺癌疫苗
  • 批准号:
    9047279
  • 财政年份:
    2013
  • 资助金额:
    $ 42.59万
  • 项目类别:
Building the Hematopoietic Stem Cell Niche
建立造血干细胞生态位
  • 批准号:
    8137505
  • 财政年份:
    2011
  • 资助金额:
    $ 42.59万
  • 项目类别:
Building the Hematopoietic Stem Cell Niche
建立造血干细胞生态位
  • 批准号:
    8704933
  • 财政年份:
    2011
  • 资助金额:
    $ 42.59万
  • 项目类别:

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ATTAC 时间:针对 gp100 细胞的 T 细胞过继转移来治疗 LAM
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自体叶酸受体-α重定向CAR T细胞过继转移治疗卵巢癌的I期临床试验
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调节性 T 细胞 (Treg) 和低剂量白细胞介素 2 (IL-2) 过继转移治疗慢性移植物抗宿主病 (GVHD) 的 I 期临床研究:基因标记为合理的联合治疗提供信息
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