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  1. Article ; Online: Injectable hydrogels for personalized cancer immunotherapies.

    Mohaghegh, Neda / Ahari, Amir / Zehtabi, Fatemeh / Buttles, Claire / Davani, Saya / Hoang, Hanna / Tseng, Kaylee / Zamanian, Benjamin / Khosravi, Safoora / Daniali, Ariella / Kouchehbaghi, Negar Hosseinzadeh / Thomas, Isabel / Serati Nouri, Hamed / Khorsandi, Danial / Abbasgholizadeh, Reza / Akbari, Mohsen / Patil, Rameshwar / Kang, Heemin / Jucaud, Vadim /
    Khademhosseini, Ali / Hassani Najafabadi, Alireza

    Acta biomaterialia

    2023  Volume 172, Page(s) 67–91

    Abstract: The field of cancer immunotherapy has shown significant growth, and researchers are now focusing on effective strategies to enhance and prolong local immunomodulation. Injectable hydrogels (IHs) have emerged as versatile platforms for encapsulating and ... ...

    Abstract The field of cancer immunotherapy has shown significant growth, and researchers are now focusing on effective strategies to enhance and prolong local immunomodulation. Injectable hydrogels (IHs) have emerged as versatile platforms for encapsulating and controlling the release of small molecules and cells, drawing significant attention for their potential to enhance antitumor immune responses while inhibiting metastasis and recurrence. IHs delivering natural killer (NK) cells, T cells, and antigen-presenting cells (APCs) offer a viable method for treating cancer. Indeed, it can bypass the extracellular matrix and gradually release small molecules or cells into the tumor microenvironment, thereby boosting immune responses against cancer cells. This review provides an overview of the recent advancements in cancer immunotherapy using IHs for delivering NK cells, T cells, APCs, chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. First, we introduce IHs as a delivery matrix, then summarize their applications for the local delivery of small molecules and immune cells to elicit robust anticancer immune responses. Additionally, we discuss recent progress in IHs systems used for local combination therapy, including chemoimmunotherapy, radio-immunotherapy, photothermal-immunotherapy, photodynamic-immunotherapy, and gene-immunotherapy. By comprehensively examining the utilization of IHs in cancer immunotherapy, this review aims to highlight the potential of IHs as effective carriers for immunotherapy delivery, facilitating the development of innovative strategies for cancer treatment. In addition, we demonstrate that using hydrogel-based platforms for the targeted delivery of immune cells, such as NK cells, T cells, and dendritic cells (DCs), has remarkable potential in cancer therapy. These innovative approaches have yielded substantial reductions in tumor growth, showcasing the ability of hydrogels to enhance the efficacy of immune-based treatments. STATEMENT OF SIGNIFICANCE: As cancer immunotherapy continues to expand, the mode of therapeutic agent delivery becomes increasingly critical. This review spotlights the forward-looking progress of IHs, emphasizing their potential to revolutionize localized immunotherapy delivery. By efficiently encapsulating and controlling the release of essential immune components such as T cells, NK cells, APCs, and various therapeutic agents, IHs offer a pioneering pathway to amplify immune reactions, moderate metastasis, and reduce recurrence. Their adaptability further shines when considering their role in emerging combination therapies, including chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. Understanding IHs' significance in cancer therapy is essential, suggesting a shift in cancer treatment dynamics and heralding a novel period of focused, enduring, and powerful therapeutic strategies.
    MeSH term(s) Humans ; Hydrogels/therapeutic use ; Immunotherapy/methods ; Neoplasms/pathology ; T-Lymphocytes ; Combined Modality Therapy ; Tumor Microenvironment
    Chemical Substances Hydrogels
    Language English
    Publishing date 2023-10-06
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2173841-5
    ISSN 1878-7568 ; 1742-7061
    ISSN (online) 1878-7568
    ISSN 1742-7061
    DOI 10.1016/j.actbio.2023.10.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: M2 isoform of pyruvate kinase rewires glucose metabolism during radiation therapy to promote an antioxidant response and glioblastoma radioresistance.

    Bailleul, Justine / Ruan, Yangjingyi / Abdulrahman, Lobna / Scott, Andrew J / Yazal, Taha / Sung, David / Park, Keunseok / Hoang, Hanna / Nathaniel, Juan / Chu, Fang-I / Palomera, Daisy / Sehgal, Anahita / Tsang, Jonathan E / Nathanson, David A / Xu, Shili / Park, Junyoung O / Ten Hoeve, Johanna / Bhat, Kruttika / Qi, Nathan /
    Kornblum, Harley I / Schaue, Dorthe / McBride, William H / Lyssiotis, Costas A / Wahl, Daniel R / Vlashi, Erina

    Neuro-oncology

    2023  Volume 25, Issue 11, Page(s) 1989–2000

    Abstract: Background: Resistance to existing therapies is a significant challenge in improving outcomes for glioblastoma (GBM) patients. Metabolic plasticity has emerged as an important contributor to therapy resistance, including radiation therapy (RT). Here, we ...

    Abstract Background: Resistance to existing therapies is a significant challenge in improving outcomes for glioblastoma (GBM) patients. Metabolic plasticity has emerged as an important contributor to therapy resistance, including radiation therapy (RT). Here, we investigated how GBM cells reprogram their glucose metabolism in response to RT to promote radiation resistance.
    Methods: Effects of radiation on glucose metabolism of human GBM specimens were examined in vitro and in vivo with the use of metabolic and enzymatic assays, targeted metabolomics, and FDG-PET. Radiosensitization potential of interfering with M2 isoform of pyruvate kinase (PKM2) activity was tested via gliomasphere formation assays and in vivo human GBM models.
    Results: Here, we show that RT induces increased glucose utilization by GBM cells, and this is accompanied with translocation of GLUT3 transporters to the cell membrane. Irradiated GBM cells route glucose carbons through the pentose phosphate pathway (PPP) to harness the antioxidant power of the PPP and support survival after radiation. This response is regulated in part by the PKM2. Activators of PKM2 can antagonize the radiation-induced rewiring of glucose metabolism and radiosensitize GBM cells in vitro and in vivo.
    Conclusions: These findings open the possibility that interventions designed to target cancer-specific regulators of metabolic plasticity, such as PKM2, rather than specific metabolic pathways, have the potential to improve the radiotherapeutic outcomes in GBM patients.
    MeSH term(s) Humans ; Pyruvate Kinase/metabolism ; Glioblastoma/metabolism ; Antioxidants ; Protein Isoforms ; Glucose/metabolism ; Cell Line, Tumor
    Chemical Substances Pyruvate Kinase (EC 2.7.1.40) ; Antioxidants ; Protein Isoforms ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2023-06-04
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2028601-6
    ISSN 1523-5866 ; 1522-8517
    ISSN (online) 1523-5866
    ISSN 1522-8517
    DOI 10.1093/neuonc/noad103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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