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    CELL-BASED CANCER VACCINES AND CANCER THERAPIES
    1.
    发明申请
    CELL-BASED CANCER VACCINES AND CANCER THERAPIES 审中-公开

    公开(公告)号：WO2021108025A1

    公开(公告)日：2021-06-03

    申请号：PCT/US2020/052775

    申请日：2020-09-25

    Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

    Inventor： IRVINE, Darrell ,  YAFFE, Michael ,  SRIRAM, Ganapathy ,  MILLING, Lauren

    IPC: A61K39/00 ,  C12N5/09 ,  G01N33/50 ,  A61P35/00

    Abstract: Described are cell-based cancer vaccines and anti-cancer immunotherapies. The vaccines include isolated tumor cells activated with one or more genotoxic drugs, and, optionally, treated with one or more MK2 inhibitors. The activated cells are highly immunogenic non-proliferative cells, and may be tested for immunogenicity ex vivo for priming T cells by co-incubating the isolated activated cells with dendritic cells and T cells. The vaccines are typically administered into patient's tumor to provide an intratumoral immune activation. Immune checkpoint inhibitor(s) (ICI) may be administered before, during, or after vaccine administration. ICI may be a component of the vaccine. The vaccines confer heightened cytotoxic immune response against the cancer cells, induce tumor regression, and enhance survival from cancer. The vaccines prevent tumor recurrence and induce a long-lasting anti-tumor immunological memory.

    PROTEIN-CHAPERONED T-CELL VACCINES
    5.
    发明申请
    PROTEIN-CHAPERONED T-CELL VACCINES 审中-公开
    蛋白质辅助的T细胞疫苗

    公开(公告)号：WO2017155981A1

    公开(公告)日：2017-09-14

    申请号：PCT/US2017/021136

    申请日：2017-03-07

    Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

    Inventor： IRVINE, Darrell ,  WITTRUP, Karl, Dane ,  MEHTA, Naveen, K. ,  RAKHRA, Kavya ,  ZHU, Eric, Franklin

    IPC: A61K39/00 ,  A61K39/39

    Abstract: Protein antigens are provided. The protein antigens typically include a peptide antigen conjugated or fused to a chaperone protein to form a "chaperone-antigen" that increases lymph node uptake; improves an immune response; or a combination thereof relative to the peptide antigen alone. The immune response can be, for example, increased antigen-specific proliferation, enhanced cytokine production, stimulation of differentiation and/or effector functions, promotion of survival, rescue from exhaustion and/or anergy of T cells, or a combination thereof. Chaperon-antigens can also be used to induce tolerance and increase immune suppressive responses. In the most preferred embodiments, the peptide antigen is fused to the chaperone protein to form a fusion protein. The "chaperone-antigen" can be combined with an adjuvant to form a vaccine and administered to a subject to modulate an immune response to the antigen. Methods of increasing immune responses, treating cancer and infectious diseases and inducing tolerance are also provided.

    Abstract translation: 提供蛋白质抗原。 蛋白质抗原通常包括与分子伴侣蛋白缀合或融合以形成“分子伴侣 - 抗原”的肽抗原。 增加淋巴结摄取; 改善免疫反应; 或其相对于单独的肽抗原的组合。 免疫应答可以是例如增加的抗原特异性增殖，增强的细胞因子产生，刺激分化和/或效应器功能，促进存活，从T细胞耗尽和/或无反应性挽救，或其组合。 伴侣抗原也可用于诱导耐受并增加免疫抑制反应。 在最优选的实施方案中，肽抗原与伴侣蛋白融合形成融合蛋白。 “分子伴侣 - 抗原” 可与佐剂组合以形成疫苗并施用于受试者以调节对抗原的免疫应答。 还提供了增加免疫应答，治疗癌症和感染性疾病以及诱导耐受性的方法。

    METHOD AND APPARATUS FOR TRACKING CELL IDENTITY
    6.
    发明申请
    METHOD AND APPARATUS FOR TRACKING CELL IDENTITY 审中-公开
    跟踪细胞识别的方法和装置

    公开(公告)号：WO2015061719A1

    公开(公告)日：2015-04-30

    申请号：PCT/US2014/062231

    申请日：2014-10-24

    Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

    Inventor： CASTELLARNAU, Marc ,  SZETO, Gregory, Lee ,  IRVINE, Darrell ,  LOVE, John, Christopher ,  VOLDMAN, Joel

    IPC: C12Q1/68

    CPC classification number: G01N15/1463 ,  G01N15/10 ,  G01N15/1484 ,  G01N35/00732 ,  G01N2015/0065 ,  G01N2015/008 ,  G01N2015/1006 ,  G01N2015/149 ,  G01N2035/00811 ,  G01N2035/00831

    Abstract: A method of tracking cell identity across analytical platforms uses stochastic barcoding (SB). SB uses a randomly generated code based on one or more of the number, color and position of beads encapsulated together with a set of cells of interest. SB use is demonstrated in an application where cells are transferred from a microwell array into a microtitre plate while keeping their identity, and obtained an average identification accuracy of 96% for transfer of 100 blocks. Model scaling of the method up to 1000 blocks demonstrated that SB is able to achieve approximately 90% accuracy.

    Abstract translation: 通过分析平台跟踪细胞身份的方法使用随机条形码（SB）。 SB使用随机生成的代码，其基于与感兴趣的一组单元格一起封装的珠的数量，颜色和位置中的一个或多个。 SB的使用在其中将细胞从微孔阵列转移到微量滴定板同时保持其同一性的应用中得到证明，并且获得了100个块的转移的平均识别精度为96％。 该方法的模型缩放高达1000块，证明SB能够实现大约90％的精度。

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