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525 results on '"Epstein, Alan L."'

1. Eliciting anti-cancer immunity by genetically engineered multifunctional exosomes

Author

Cheng, Qinqin, Dai, Zhefu, Smbatyan, Goar, Epstein, Alan L, Lenz, Heinz-Josef, and Zhang, Yong

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Immunotherapy, Breast Cancer, Immunization, Bioengineering, Women's Health, Nanotechnology, Vaccine Related, Biotechnology, Cancer, 5.1 Pharmaceuticals, 5.2 Cellular and gene therapies, Animals, Antineoplastic Agents, Immunological, ErbB Receptors, Exosomes, Humans, Mice, Triple Negative Breast Neoplasms, exosomes, extracellular vesicles, immunotherapy, protein engineering, synthetic biology, triple negative breast cancer, Biological Sciences, Technology, Medical and Health Sciences, Genetics, Clinical sciences, Medical biotechnology
Abstract

Exosomes are cell-derived nanovesicles involved in regulating intercellular communications. In contrast to conventional nanomedicines, exosomes are characterized by unique advantages for therapeutic development. Despite their major successes in drug delivery, the full potential of exosomes for immunotherapy remains untapped. Herein we designed genetically engineered exosomes featured with surfaced-displayed antibody targeting groups and immunomodulatory proteins. Through genetic fusions with exosomal membrane proteins, Expi293F cell-derived exosomes were armed with monoclonal antibodies specific for human T-cell CD3 and epidermal growth factor receptor (EGFR) as well as immune checkpoint modulators, programmed death 1 (PD-1) and OX40 ligand (OX40L). The resulting genetically engineered multifunctional immune-modulating exosomes (GEMINI-Exos) can not only redirect and activate T cells toward killing EGFR-positive triple negative breast cancer (TNBC) cells but also elicit robust anti-cancer immunity, giving rise to highly potent inhibition against established TNBC tumors in mice. GEMINI-Exos represent candidate agents for immunotherapy and may offer a general strategy for generating exosome-based immunotherapeutics with desired functions and properties.

Published
2022

3. Critical role of OX40 signaling in the TCR-independent phase of human and murine thymic Treg generation

Author

Kumar, Prabhakaran, Marinelarena, Alejandra, Raghunathan, Divya, Ragothaman, Vandhana K, Saini, Shikha, Bhattacharya, Palash, Fan, Jilao, Epstein, Alan L, Maker, Ajay V, and Prabhakar, Bellur S

Subjects
Biomedical and Clinical Sciences, Immunology, Autoimmune Disease, Underpinning research, 1.1 Normal biological development and functioning, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Animals, Cell Proliferation, Cells, Cultured, Cytokines, Female, Forkhead Transcription Factors, Humans, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell, Receptors, OX40, Signal Transduction, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Thymocytes, IL-2, OX40L, Thymic Tregs, Treg proliferation, maturation, Biochemistry and Cell Biology
Abstract

Regulatory T cells (Tregs) play a pivotal role in immune-tolerance, and loss of Treg function can lead to the development of autoimmunity. Natural Tregs generated in the thymus substantially contribute to the Treg pool in the periphery, where they suppress self-reactive effector T cells (Teff) responses. Recently, we showed that OX40L (TNFSF4) is able to drive selective proliferation of peripheral Tregs independent of canonical antigen presentation (CAP-independent) in the presence of low-dose IL-2. Therefore, we hypothesized that OX40 signaling might be integral to the TCR-independent phase of murine and human thymic Treg (tTreg) development. Development of tTregs is a two-step process: Strong T-cell receptor (TCR) signals in combination with co-signals from the TNFRSF members facilitate tTreg precursor selection, followed by a TCR-independent phase of tTreg development in which their maturation is driven by IL-2. Therefore, we investigated whether OX40 signaling could also play a critical role in the TCR-independent phase of tTreg development. OX40-/- mice had significantly reduced numbers of CD25-Foxp3low tTreg precursors and CD25+Foxp3+ mature tTregs, while OX40L treatment of WT mice induced significant proliferation of these cell subsets. Relative to tTeff cells, OX40 was expressed at higher levels in both murine and human tTreg precursors and mature tTregs. In ex vivo cultures, OX40L increased tTreg maturation and induced CAP-independent proliferation of both murine and human tTregs, which was mediated through the activation of AKT-mTOR signaling. These novel findings show an evolutionarily conserved role for OX40 signaling in tTreg development and proliferation, and might enable the development of novel strategies to increase Tregs and suppress autoimmunity.

Published
2019

4. PKC-ѳ is dispensable for OX40L-induced TCR-independent Treg proliferation but contributes by enabling IL-2 production from effector T-cells.

Author

Alharshawi, Khaled, Marinelarena, Alejandra, Kumar, Prabhakaran, El-Sayed, Osama, Bhattacharya, Palash, Sun, Zuoming, Epstein, Alan L, Maker, Ajay V, and Prabhakar, Bellur S

Subjects
Animals, Mice, Knockout, Mice, Tumor Necrosis Factors, NF-kappa B, Membrane Glycoproteins, Interleukin-2, Cell Proliferation, T-Lymphocytes, Regulatory, Receptors, OX40, Protein Kinase C-theta, OX40 Ligand
Abstract

We have previously shown that OX40L/OX40 interaction is critical for TCR-independent selective proliferation of Foxp3+ Tregs, but not Foxp3- effector T-cells (Teff), when CD4+ T-cells are co-cultured with GM-CSF derived bone marrow dendritic cells (G-BMDCs). Events downstream of OX40L/OX40 interaction in Tregs responsible for this novel mechanism are not understood. Earlier, OX40L/OX40 interaction has been shown to stimulate CD4+ T-cells through the formation of a signalosome involving TRAF2/PKC-Ѳ leading to NF-kB activation. In this study, using CD4+ T-cells from WT and OX40-/- mice we first established that OX40 mediated activation of NF-kB was critical for this Treg proliferation. Although CD4+ T-cells from PKC-Ѳ-/- mice were also defective in G-BMDC induced Treg proliferation ex vivo, this defect could be readily corrected by adding exogenous IL-2 to the co-cultures. Furthermore, by treating WT, OX40-/-, and PKC-Ѳ-/- mice with soluble OX40L we established that OX40L/OX40 interaction was required and sufficient to induce Treg proliferation in vivo independent of PKC-Ѳ status. Although PKC-Ѳ is dispensable for TCR-independent Treg proliferation per se, it is essential for optimum IL-2 production by Teff cells. Finally, our findings suggest that OX40L binding to OX40 likely results in recruitment of TRAF1 for downstream signalling.

Published
2017

13. Combination immunotherapy with anti-CD20 and anti-HLA-DR monoclonal antibodies induces synergistic anti-lymphoma effects in human lymphoma cell lines

Author

Tobin, Evan, Denardo, Gerald, Zhang, Nan, Epstein, Alan L, Liu, Cathy, and Denardo, Sally

Subjects
lymphoma, immunotherapy, rituximab, lym-1, CD20, HLA-DR
Abstract

Rituximab is effective in about one half of patients with indolent lymphoma. Even these patients relapse and develop rituximab resistance. To increase potency and circumvent resistance, the anti-lymphoma effects of rituximab, an anti-CD20 MAb(1), combined with chLym-1(2), an anti-HLA-DR MAb, were assessed in human lymphoma cell lines by examining growth inhibition and cell death, apoptosis induction, ADCC(3) and CDC4. There were additive effects in all assays and synergism in cell lines, such as B35M, which displayed resistance to either MAb alone. In B35M cells, combined rituximab and chLym-1 induced a 27-fold direct reduction in viable cells, whereas equivalent concentrations of rituximab or chLym-1 alone induced only a 1-fold and 10-fold reduction in viable cells, respectively. Because these results occurred at MAb concentrations readily achievable in patients, they suggest that this combination immunotherapy regimen may increase the potency and range of effectiveness of these MAbs in lymphoma patients.

Published
2007

16. Data from NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment

Author

Dong, Tiange, primary, Dave, Priyal, primary, Yoo, EunJeong, primary, Ebright, Brandon, primary, Ahluwalia, Kabir, primary, Zhou, Eugene, primary, Asante, Isaac, primary, Salimova, Malika, primary, Pei, Hua, primary, Lin, Tracey, primary, Mead, Andrew, primary, Li, Zeyang, primary, Humayun, Mark, primary, Petasis, Nicos A., primary, Epstein, Alan L., primary, and Louie, Stan G., primary

Published
2023
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17. Supplementary Tables from NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment

Author

Dong, Tiange, primary, Dave, Priyal, primary, Yoo, EunJeong, primary, Ebright, Brandon, primary, Ahluwalia, Kabir, primary, Zhou, Eugene, primary, Asante, Isaac, primary, Salimova, Malika, primary, Pei, Hua, primary, Lin, Tracey, primary, Mead, Andrew, primary, Li, Zeyang, primary, Humayun, Mark, primary, Petasis, Nicos A., primary, Epstein, Alan L., primary, and Louie, Stan G., primary

Published
2023
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18. Supplementary Figure S3 from NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment

Author

Dong, Tiange, primary, Dave, Priyal, primary, Yoo, EunJeong, primary, Ebright, Brandon, primary, Ahluwalia, Kabir, primary, Zhou, Eugene, primary, Asante, Isaac, primary, Salimova, Malika, primary, Pei, Hua, primary, Lin, Tracey, primary, Mead, Andrew, primary, Li, Zeyang, primary, Humayun, Mark, primary, Petasis, Nicos A., primary, Epstein, Alan L., primary, and Louie, Stan G., primary

Published
2023
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19. Supplementary Figure 2 from An In Vivo Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

Author

Murphy, Katherine A., primary, Lechner, Melissa G., primary, Popescu, Flavia E., primary, Bedi, Jessica, primary, Decker, Stacy A., primary, Hu, Peisheng, primary, Erickson, Jami R., primary, O'Sullivan, M. Gerard, primary, Swier, Lauryn, primary, Salazar, Andres M., primary, Olin, Michael R., primary, Epstein, Alan L., primary, and Ohlfest, John R., primary

Published
2023
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20. Supplementary Figure 6 from An In Vivo Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

Author

Murphy, Katherine A., primary, Lechner, Melissa G., primary, Popescu, Flavia E., primary, Bedi, Jessica, primary, Decker, Stacy A., primary, Hu, Peisheng, primary, Erickson, Jami R., primary, O'Sullivan, M. Gerard, primary, Swier, Lauryn, primary, Salazar, Andres M., primary, Olin, Michael R., primary, Epstein, Alan L., primary, and Ohlfest, John R., primary

Published
2023
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22. Supplementary Figure 5 from An In Vivo Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

Author

Murphy, Katherine A., primary, Lechner, Melissa G., primary, Popescu, Flavia E., primary, Bedi, Jessica, primary, Decker, Stacy A., primary, Hu, Peisheng, primary, Erickson, Jami R., primary, O'Sullivan, M. Gerard, primary, Swier, Lauryn, primary, Salazar, Andres M., primary, Olin, Michael R., primary, Epstein, Alan L., primary, and Ohlfest, John R., primary

Published
2023
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27. Supplementary Figure 1 from An In Vivo Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

Author

Murphy, Katherine A., primary, Lechner, Melissa G., primary, Popescu, Flavia E., primary, Bedi, Jessica, primary, Decker, Stacy A., primary, Hu, Peisheng, primary, Erickson, Jami R., primary, O'Sullivan, M. Gerard, primary, Swier, Lauryn, primary, Salazar, Andres M., primary, Olin, Michael R., primary, Epstein, Alan L., primary, and Ohlfest, John R., primary

Published
2023
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28. Supplementary Figure 3 from An In Vivo Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

Author

Murphy, Katherine A., primary, Lechner, Melissa G., primary, Popescu, Flavia E., primary, Bedi, Jessica, primary, Decker, Stacy A., primary, Hu, Peisheng, primary, Erickson, Jami R., primary, O'Sullivan, M. Gerard, primary, Swier, Lauryn, primary, Salazar, Andres M., primary, Olin, Michael R., primary, Epstein, Alan L., primary, and Ohlfest, John R., primary

Published
2023
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32. Supplementary Figure Legend from An In Vivo Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

Author

Murphy, Katherine A., primary, Lechner, Melissa G., primary, Popescu, Flavia E., primary, Bedi, Jessica, primary, Decker, Stacy A., primary, Hu, Peisheng, primary, Erickson, Jami R., primary, O'Sullivan, M. Gerard, primary, Swier, Lauryn, primary, Salazar, Andres M., primary, Olin, Michael R., primary, Epstein, Alan L., primary, and Ohlfest, John R., primary

Published
2023
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33. Supplementary Figure 4 from An In Vivo Immunotherapy Screen of Costimulatory Molecules Identifies Fc-OX40L as a Potent Reagent for the Treatment of Established Murine Gliomas

Author

Murphy, Katherine A., primary, Lechner, Melissa G., primary, Popescu, Flavia E., primary, Bedi, Jessica, primary, Decker, Stacy A., primary, Hu, Peisheng, primary, Erickson, Jami R., primary, O'Sullivan, M. Gerard, primary, Swier, Lauryn, primary, Salazar, Andres M., primary, Olin, Michael R., primary, Epstein, Alan L., primary, and Ohlfest, John R., primary

Published
2023
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39. LINC00261expression reduces mutation accumulation while conferring resistance to cisplatin and altering the tumor-immune microenvironment in lung adenocarcinoma

Author

Castillo, Jonathan, primary, Xue, Tianchun, additional, Joseph, Samantha, additional, Norwood, Mayela, additional, Mullen, Daniel J., additional, Berrellez, Stephanie, additional, James, Sophia, additional, Epstein, Alan L., additional, McEachron, Troy, additional, and Marconett, Crystal N., additional

Published
2023
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40. Enhanced brain entry of checkpoint-inhibitory therapeutic antibodies facilitated by intraarterial NEO100 in mouse models of brain-localized malignancies

Author

Wang, Weijun, primary, He, Haiping, additional, Zeng, Shan, additional, Cho, Hee-Yeon, additional, Minea, Radu O., additional, Swenson, Steven D., additional, Zheng, Long, additional, Epstein, Alan L., additional, Stathopoulos, Apostolos, additional, Chen, Ligang, additional, Schönthal, Axel H., additional, and Chen, Thomas C., additional

Published
2023
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45. Targetable vulnerabilities in T- and NK-cell lymphomas identified through preclinical models

Author

Ng, Samuel Y., Yoshida, Noriaki, Christie, Amanda L., Ghandi, Mahmoud, Dharia, Neekesh V., Dempster, Joshua, Murakami, Mark, Shigemori, Kay, Morrow, Sara N., Van Scoyk, Alexandria, Cordero, Nicolas A., Stevenson, Kristen E., Puligandla, Maneka, Haas, Brian, Lo, Christopher, Meyers, Robin, Gao, Galen, Cherniack, Andrew, Louissaint, Jr, Abner, Nardi, Valentina, Thorner, Aaron R., Long, Henry, Qiu, Xintao, Morgan, Elizabeth A., Dorfman, David M., Fiore, Danilo, Jang, Julie, Epstein, Alan L., Dogan, Ahmet, Zhang, Yanming, Horwitz, Steven M., Jacobsen, Eric D., Santiago, Solimar, Ren, Jian-Guo, Guerlavais, Vincent, Annis, D. Allen, Aivado, Manuel, Saleh, Mansoor N., Mehta, Amitkumar, Tsherniak, Aviad, Root, David, Vazquez, Francisca, Hahn, William C., Inghirami, Giorgio, Aster, Jon C., Weinstock, David M., and Koch, Raphael

Published
2018
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