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  1. Article ; Online: Drug delivery for metabolism targeted cancer immunotherapy.

    Khodaei, Taravat / Inamdar, Sahil / Suresh, Abhirami P / Acharya, Abhinav P

    Advanced drug delivery reviews

    2022  Volume 184, Page(s) 114242

    Abstract: Drug delivery vehicles have made a great impact on cancer immunotherapies in clinics and pre-clinical research. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of ... ...

    Abstract Drug delivery vehicles have made a great impact on cancer immunotherapies in clinics and pre-clinical research. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of several successful companies and clinical products. Interestingly, these drug delivery modalities not only modulate the function of immune cells (often quantified at the mRNA and protein levels), but also modulate the metabolism of these cells. Specifically, cancer immunotherapy often leads to activation of different immune cells such as dendritic cells, macrophages and T cells, which is driven by energy metabolism of these cells. Recently, there has been a great excitement about interventions that can directly modulate the energy metabolism of these immune cells and thus affect their function and in turn lead to a robust cancer immune response. Here we review few strategies that have been tested in clinic and pre-clinical research for generating effective metabolism-associated cancer therapies and immunotherapies.
    MeSH term(s) Cancer Vaccines/therapeutic use ; Drug Delivery Systems ; Humans ; Immunotherapy ; Neoplasms/drug therapy ; T-Lymphocytes
    Chemical Substances Cancer Vaccines
    Language English
    Publishing date 2022-03-31
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 639113-8
    ISSN 1872-8294 ; 0169-409X
    ISSN (online) 1872-8294
    ISSN 0169-409X
    DOI 10.1016/j.addr.2022.114242
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2241: Show issues Location:
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  2. Article: Exponentially decreasing exposure of antigen generates anti-inflammatory T-cell responses.

    Esrafili, Arezoo / Kupfer, Joshua / Thumsi, Abhirami / Jaggarapu, Madhan Mohan Chandra Sekhar / Suresh, Abhirami P / Talitckii, Aleksandr / Khodaei, Taravat / Swaminathan, Srivatsan J / Mantri, Shivani / Peet, Matthew M / Acharya, Abhinav P

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Rheumatoid Arthritis (RA) is a chronic debilitating disease characterized by auto-immune reaction towards self-antigen such as collagen type II. In this study, we investigated the impact of exponentially decreasing levels of antigen exposure on pro- ... ...

    Abstract Rheumatoid Arthritis (RA) is a chronic debilitating disease characterized by auto-immune reaction towards self-antigen such as collagen type II. In this study, we investigated the impact of exponentially decreasing levels of antigen exposure on pro-inflammatory T cell responses in the collagen-induced arthritis (CIA) mouse model. Using a controlled delivery experimental approach, we manipulated the collagen type II (CII) antigen concentration presented to the immune system. We observed that exponentially decreasing levels of antigen generated reduced pro-inflammatory T cell responses in secondary lymphoid organs in mice suffering from RA. Specifically, untreated mice exhibited robust pro-inflammatory T cell activation and increased paw inflammation, whereas, mice exposed to exponentially decreasing concentrations of CII demonstrated significantly reduced pro-inflammatory T cell responses, exhibited lower levels of paw inflammation, and decreased arthritis scores in right rear paw. The data also demonstrate that the decreasing antigen levels promoted the induction of regulatory T cells (Tregs), which play a crucial role in maintaining immune tolerance and suppressing excessive inflammatory responses. Our findings highlight the importance of antigen concentration in modulating pro-inflammatory T cell responses in the CIA model. These results provide valuable insights into the potential therapeutic strategies that target antigen presentation to regulate immune responses and mitigate inflammation in rheumatoid arthritis and other autoimmune diseases. Further investigations are warranted to elucidate the specific mechanisms underlying the antigen concentration-dependent modulation of T cell responses and to explore the translational potential of this approach for the development of novel therapeutic interventions in autoimmune disorders.
    Language English
    Publishing date 2023-09-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.15.558014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Orally delivered 2D covalent organic frameworks releasing kynurenine generate anti-inflammatory T cell responses in collagen induced arthritis mouse model.

    Mohan Chandra Sekhar Jaggarapu, Madhan / Thumsi, Abhirami / Nile, Richard / D Ridenour, Brian / Khodaei, Taravat / P Suresh, Abhirami / Esrafili, Arezoo / Jin, Kailong / P Acharya, Abhinav

    Biomaterials

    2023  Volume 300, Page(s) 122204

    Abstract: Covalent organic framework (COF) crystalline biomaterials have great potential for drug delivery since they can load large amounts of small molecules (e.g. metabolites) and release them in a controlled manner, as compared to their amorphous counterparts. ...

    Abstract Covalent organic framework (COF) crystalline biomaterials have great potential for drug delivery since they can load large amounts of small molecules (e.g. metabolites) and release them in a controlled manner, as compared to their amorphous counterparts. Herein, we screened different metabolites for their ability to modulate T cell responses in vitro and identified Kynurenine (KyH) as a key metabolite that not only decreases frequency of pro-inflammatory RORgt + T cells but also supports frequency of anti-inflammatory GATA3+ T cells. Moreover, we developed a methodology to generate imine-based TAPB-PDA COF at room temperature and loaded these COFs with KyH. KyH loaded COFs (COF-KyH) were able to then release KyH in a controlled manner for 5 days in vitro. Notably, COF-KyH when delivered orally in mice induced with collagen-induced rheumatoid arthritis (CIA) were able to increase frequency of anti-inflammatory GATA3+CD8
    MeSH term(s) Animals ; Mice ; Arthritis, Experimental/drug therapy ; Kynurenine ; Metal-Organic Frameworks ; CD8-Positive T-Lymphocytes ; Disease Models, Animal ; Excipients
    Chemical Substances Kynurenine (343-65-7) ; Metal-Organic Frameworks ; Excipients
    Language English
    Publishing date 2023-06-13
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2023.122204
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 2371: Show issues Location:
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  4. Article ; Online: Succinate in the tumor microenvironment affects tumor growth and modulates tumor associated macrophages.

    Inamdar, Sahil / Suresh, Abhirami P / Mangal, Joslyn L / Ng, Nathan D / Sundem, Alison / Behbahani, Hoda Shokrollahzadeh / Rubino, Thomas E / Yaron, Jordan R / Khodaei, Taravat / Green, Matthew / Curtis, Marion / Acharya, Abhinav P

    Biomaterials

    2023  Volume 301, Page(s) 122292

    Abstract: Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of ... ...

    Abstract Succinate is an important metabolite that modulates metabolism of immune cells and cancer cells in the tumor microenvironment (TME). Herein, we report that polyethylene succinate (PES) microparticles (MPs) biomaterial mediated controlled delivery of succinate in the TME modulates macrophage responses. Administering PES MPs locally with or without a BRAF inhibitor systemically in an immune-defective aging mice with clinically relevant BRAF
    MeSH term(s) Animals ; Mice ; Succinic Acid ; Tumor-Associated Macrophages ; Tumor Microenvironment ; Proto-Oncogene Proteins B-raf ; Succinates ; Melanoma
    Chemical Substances Succinic Acid (AB6MNQ6J6L) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; poly(ethylene succinate) ; Succinates
    Language English
    Publishing date 2023-08-26
    Publishing country Netherlands
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 603079-8
    ISSN 1878-5905 ; 0142-9612
    ISSN (online) 1878-5905
    ISSN 0142-9612
    DOI 10.1016/j.biomaterials.2023.122292
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice.

    Inamdar, Sahil / Suresh, Abhirami P / Mangal, Joslyn L / Ng, Nathan D / Sundem, Alison / Wu, Christopher / Lintecum, Kelly / Thumsi, Abhirami / Khodaei, Taravat / Halim, Michelle / Appel, Nicole / Jaggarapu, Madhan Mohan Chandra Sekhar / Esrafili, Arezoo / Yaron, Jordan R / Curtis, Marion / Acharya, Abhinav P

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 5333

    Abstract: Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 ( ... ...

    Abstract Inhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.1 tumours in immunocompetent female mice. Furthermore, to test the versatility of this strategy, adoptive DC therapy is developed with formulations that incorporate F16BP, poly(IC) as adjuvant and mRNA derived from B16F10 cells as antigens in established B16F10 tumours in immunocompetent female mice. F16BP vaccine formulations rescue DCs in vitro and in vivo, significantly improve the survival of mice, and generate cytotoxic T cell (Tc) responses by elevating Tc1 and Tc17 cells within the tumour. Overall, these results demonstrate that rescuing glycolysis of DCs using metabolite-based formulations can be utilized to generate immunotherapy even in the presence of glycolytic inhibitor.
    MeSH term(s) Female ; Animals ; Mice ; Immunotherapy ; Glycolysis ; Adjuvants, Immunologic/pharmacology ; Fructose ; Poly I-C ; Dendritic Cells ; Neoplasms
    Chemical Substances Adjuvants, Immunologic ; Fructose (30237-26-4) ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 2023-09-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-41016-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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