Overcoming vaccine-associated hypoxia with advanced biomaterials to enhance cancer immunotherapy

利用先进生物材料克服疫苗相关缺氧以增强癌症免疫治疗

基本信息

  • 批准号:
    10612093
  • 负责人:
  • 金额:
    $ 45.1万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

Project Summary Overcoming the poor efficacy of tumor cell vaccines will require enhancing activation of the immune system and preventing an immunosuppressive tumor microenvironment such as local hypoxia. In this proposal, we will address this critical need by engineering tumor cell vaccines with advanced oxygen-releasing biomaterials (O2- cryogels) to combat hypoxia-driven immunosuppression and improve antitumor immune responses in relevant mouse models of prostate cancer. Our preliminary data in mice indicate that: (i) O2-cryogels can reverse local hypoxia and restore the function of key immune cells (dendritic cells; DCs); (ii) once in the body, cryogel vaccines efficiently localize transplanted tumor cells, controllably release immunomodulatory factors, and recruit large numbers of DCs from the host; and (iii) elicit a specific and robust vaccine-induced T cell-mediated antitumor immunity. Here, we will optimize the characteristics of O2-cryogels for maximum antitumor efficacy and safety; and assess their ability to suppress the local hypoxic stress and improve DC recruitment, activation, and homing to the draining lymph nodes. Finally, we will test O2-cryogel vaccines in prophylactic and therapeutic mouse models of prostate cancer to determine their ability to induce specific, effective, and long-lasting antitumor immune responses. This proposal may have a sustained impact on the field by defining a new avenue of cancer immunotherapy that operates independently but synergizes with other therapies.
项目总结

项目成果

期刊论文数量(15)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Biomaterials Recycling: A Promising Pathway to Sustainability.
  • DOI:
    10.3389/fbiom.2023.1260402
  • 发表时间:
    2023-11
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Paulina Wiśniewska;M. Saeb;S. Bencherif
  • 通讯作者:
    Paulina Wiśniewska;M. Saeb;S. Bencherif
Endothelial glycocalyx sensitivity to chemical and mechanical sub-endothelial substrate properties.
Biomaterial-assisted local oxygenation safeguards the prostimulatory phenotype and functions of human dendritic cells in hypoxia.
  • DOI:
    10.3389/fimmu.2023.1278397
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    7.3
  • 作者:
  • 通讯作者:
Synthesis and Characterization of Folic Acid-Functionalized DPLA-co-PEG Nanomicelles for the Targeted Delivery of Letrozole.
  • DOI:
    10.1021/acsabm.3c00041
  • 发表时间:
    2023-05-15
  • 期刊:
  • 影响因子:
    4.7
  • 作者:
    Rostami, Neda;Gomari, Mohammad Mahmoudi;Abdouss, Majid;Moeinzadeh, Alaa;Choupani, Edris;Davarnejad, Reza;Heidari, Reza;Bencherif, Sidi A
  • 通讯作者:
    Bencherif, Sidi A
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