Journal Articles

Cytokine therapy

Treatment strategies based on cytokines, including cytokine gene therapy and immunocytokines

Reprogramming the murine colon cancer microenvironment using lentivectors encoding shRNA against IL-10 as a component of a potent DC-based chemoimmunotherapy

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BACKGROUND: The excessive amounts of immunosuppressive factors present in a tumor microenvironment (TME) reduce the effectiveness of cancer vaccines. The main objective of our research was to improve the effectiveness of dendritic cell (DC)-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors encoding shRNA specific to IL-10 (shIL10 LVs) in murine colon carcinoma MC38 model. METHODS: The efficacy of shIL10 LVs in silencing of IL-10 expression was measured both in vitro and in vivo using Real-Time PCR and ELISA assays. In addition, the influence of intratumorally inoculated lentivectors on MC38 tumor microenvironment was examined using flow cytometry method. The effect of applied therapeutic schemes was determined by measurement of tumor growth inhibition and activation state of local and systemic immune response. RESULTS: We observed that intratumorally inoculated shIL10 LVs transduced tumor and TME-infiltrating cells and reduced the secretion of IL-10. Application of shIL10 LVs for three consecutive weeks initiated tumor growth inhibition, whereas treatment with shIL10 LVs and BMDC/TAg did not enhance the antitumor effect. However, when pretreatment with CY was introduced to the proposed scheme, we noticed high MC38 tumor growth inhibition accompanied by reduction of MDSCs and Tregs in TME, as well as activation of potent local and systemic Th1-type antitumor response. CONCLUSIONS: The obtained data shows that remodeling of TME by shIL10 LVs and CY enhances DC activity and supports them during regeneration and actuation of a potent antitumor response. Therefore, therapeutic strategies aimed at local IL-10 elimination using lentiviral vectors should be further investigated in context of combined chemoimmunotherapies.

Author Info: (1) Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114, Wroclaw, Poland. joanna@iitd.pan.wroc.pl. (2) Hirszfeld Institute of Immunology

Author Info: (1) Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114, Wroclaw, Poland. joanna@iitd.pan.wroc.pl. (2) Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114, Wroclaw, Poland. (3) Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114, Wroclaw, Poland. (4) Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114, Wroclaw, Poland. (5) Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114, Wroclaw, Poland.

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Combination therapy improves immune response and prognosis in patients with advanced oral mucosal melanoma: A clinical treatment success

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OBJECTIVE: This study was undertaken to analyze disease response and immune response to assess treatment effectiveness and success in patients with advanced oral mucosal melanoma treated with cytokines injection, cryosurgery, and adoptive cell transfer therapy. STUDY DESIGN: Ten patients were enrolled in the study, and the relevant characteristics and immunologic differences were evaluated. RESULTS: All patients achieved an objective clinical response according to the Response Evaluation Criteria in Solid Tumors, including 7 cases of continuing complete remission (55, 27, 87 + , 58(+), 58 + , 45 + , and 37 + months) and 3 cases of partial remission (30, 12, and 9 months). Five responders are currently alive. After combination therapy, we observed that the proportion of CD3+ lymphocytes and the secretion of interferon-gamma increased, whereas interleukin-10 decreased. In the assay of improved cytokine-induced killer cells, CD4+CD25+ regulatory T cells declined, and natural killer cells upregulated. Meanwhile, the proliferation rate of in vitro cultured improved cytokine-induced killer cells improved after courses of therapy. CONCLUSIONS: Combination therapy of cytokine injection, cryosurgery, and transfer of improved cytokine-induced killer cells may be a promising approach for patients with oral mucosal melanoma.

Author Info: (1) Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology

Author Info: (1) Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. (2) Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. (3) Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. (4) Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. (5) Department of Oral and Maxillofacial Surgery, Clinical Laboratory, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China. Electronic address: Wanghua9@mail.sysu.edu.cn.

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IL-23 secreted by myeloid cells drives castration-resistant prostate cancer

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Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC. Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumour cells, promoting cell survival and proliferation in androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23 concentration are increased in blood and tumour samples from patients with CRPC. Antibody-mediated inactivation of IL-23 restored sensitivity to androgen-deprivation therapy in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL-23 can oppose MDSC-mediated resistance to castration in prostate cancer and synergize with standard therapies.

Author Info: (1) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (2) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona

Author Info: (1) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (2) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (3) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (4) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (5) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (6) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (7) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (8) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (9) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (10) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (11) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. (12) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (13) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (14) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (15) Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. (16) Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. (17) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (18) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (19) Department of Urology, University of Padova, Padova, Italy. (20) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (21) Division of Oncology, Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy. (22) Experimental Imaging Center, San Raffaele Scientific Institute, Milan, Italy. (23) IMED Oncology AstraZeneca, Li Ka Shing Centre, Cambridge, UK. (24) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (25) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (26) The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, UK. (27) Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland. andrea.alimonti@ior.iosi.ch. Universita della Svizzera italiana, Faculty of Biomedical Sciences, Lugano, Switzerland. andrea.alimonti@ior.iosi.ch. Faculty of Biology and Medicine, University of Lausanne UNIL, Lausanne, Switzerland. andrea.alimonti@ior.iosi.ch. Department of Medicine, Venetian Institute of Molecular Medicine, University of Padova, Padova, Italy. andrea.alimonti@ior.iosi.ch.

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IFNgamma: signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy

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IFNgamma is a cytokine with important roles in tissue homeostasis, immune and inflammatory responses and tumour immunosurveillance. Signalling by the IFNgamma receptor activates the Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) pathway to induce the expression of classical interferon-stimulated genes that have key immune effector functions. This Review focuses on recent advances in our understanding of the transcriptional, chromatin-based and metabolic mechanisms that underlie IFNgamma-mediated polarization of macrophages to an 'M1-like' state, which is characterized by increased pro-inflammatory activity and macrophage resistance to tolerogenic and anti-inflammatory factors. In addition, I describe the newly discovered effects of IFNgamma on other leukocytes, vascular cells, adipose tissue cells, neurons and tumour cells that have important implications for autoimmunity, metabolic diseases, atherosclerosis, neurological diseases and immune checkpoint blockade cancer therapy.

Author Info: (1) Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, USA. IvashkivL@HSS.EDU. Immunology and Microbial Pathogenesis

Author Info: (1) Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, USA. IvashkivL@HSS.EDU. Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, NY, USA. IvashkivL@HSS.EDU.

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TGF-beta Sustains Tumor Progression through Biochemical and Mechanical Signal Transduction

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Transforming growth factor β (TGF-β) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-β activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development is critical for designing therapeutics that inhibit tumor progression while bolstering the immune response.

Author Info: (1) Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, 413 E 69th St., Belfer Research Building, New York, NY 10021, USA. rlf2001@med.cornell.edu. (2)

Author Info: (1) Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, 413 E 69th St., Belfer Research Building, New York, NY 10021, USA. rlf2001@med.cornell.edu. (2) Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine, 413 E 69th St., Belfer Research Building, New York, NY 10021, USA. dnixon@med.cornell.edu. (3) GW Nanofabrication and Imaging Center, Office of the Vice President for Research, George Washington University, Washington, DC 20052, USA. chrisbrantner@gwu.edu. (4) GW Nanofabrication and Imaging Center, Office of the Vice President for Research, George Washington University, Washington, DC 20052, USA. anastas@gwu.edu. (5) Departments of Microbiology, Immunology and Molecular Genetics, Medicine, Pediatrics, UCLA AIDS Institute and the Jonsson Comprehensive Cancer Center, University of California, 615 Charles E. Young Drive South, BSRB2, Los Angeles, CA 90095, USA. uittenbo@ucla.edu.

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Cytokines in the Treatment of Cancer

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Cytokines are major regulators of innate and adaptive immunity that enable cells of the immune system to communicate over short distances. Cytokine therapy to activate the immune system of cancer patients has been an important treatment modality and continues to be a key contributor to current clinical cancer research. Interferon alpha (IFNalpha) is approved for adjuvant treatment of completely resected high-risk melanoma patients and several refractory malignancies. High-dose interleukin-2 (HDIL-2) is approved for treatment of metastatic renal cell cancer and melanoma, but both agents are currently less commonly used with the development of newer agents. Granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN gamma (IFNgamma), IL-7, IL-12, and IL-21 were evaluated in clinical trials and remain part of certain investigational trials. The initial single-agent clinical trials with the long-awaited IL-15 have been completed and combination trials with antitumor antibodies or checkpoint inhibitors (CPIs) have been initiated. However, cytokines in monotherapy have not fulfilled the promise of efficacy seen in preclinical experiments. They are often associated with severe dose-limiting toxicities that are manageable with appropriate dosing and are now better understood to induce immune-suppressive humoral factors, suppressive cells, and cellular checkpoints, without consistently inducing a tumor-specific response. To circumvent these impediments, cytokines are being investigated clinically with new engineered cytokine mutants (superkines), chimeric antibody-cytokine fusion proteins (immunokines), anticancer vaccines, CPIs, and cancer-directed monoclonal antibodies to increase their antibody-dependent cellular cytotoxicity or sustain cellular responses and anticancer efficacy. In this review, we summarize current knowledge and clinical application of cytokines either as monotherapy or in combination with other biological agents. We emphasize a discussion of future directions for research on these cytokines, to bring them to fruition as major contributors for the treatment of metastatic malignancy.

Author Info: (1) Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute , Bethesda, Maryland. (2) Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute

Author Info: (1) Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute , Bethesda, Maryland. (2) Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute , Bethesda, Maryland. (3) Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute , Bethesda, Maryland.

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Beyond Cell Death: New Functions for TNF Family Cytokines in Autoimmunity and Tumor Immunotherapy

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Originally discovered as an inducer of apoptosis, the TNF-family receptor Fas (CD95, APO-1, TNFRSF6) has more recently been found to have functions beyond cell death, including T cell co-stimulation and promoting terminal differentiation of CD4(+) and CD8(+) T cells. Other TNF family members also discovered as apoptosis inducers, such as TRAIL (APO-2L, TNFSF10), can promote inflammation through caspase-8. Surprisingly, non-apoptotic signaling through Fas can protect from the autoimmunity seen in Fas deficiency independently from the cell death inducing functions of the receptor. Non-apoptotic Fas signaling can induce tumor cell growth and migration, and impair the efficacy of T cell adoptive immunotherapy. Blocking of non-apoptotic functions of these receptors may be a novel strategy to regulate autoimmunity and inflammation, and enhance antitumor immunity.

Author Info: (1) Immunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (2) Immunoregulation Section

Author Info: (1) Immunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (2) Immunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (3) Immunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. (4) Center for Cell Engineering and Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, NY, 10065 USA; Parker Institute for Cancer Immunotherapy, MSKCC, New York, NY, 10065 USA; Weill Cornell Medical College, New York, NY 10065, USA. (5) Immunoregulation Section, Autoimmunity Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: siegelr@mail.nih.gov.

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(89)Zr-labeled CEA-targeted IL-2 variant immunocytokine in patients with solid tumors: CEA-mediated tumor accumulation and role of IL-2 receptor-binding

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Cergutuzumab amunaleukin (CEA-IL2v) is an immunocytokine directed against carcinoembryonic antigen (CEA) containing an IL2v-moiety with abolished IL-2 receptor (IL-2R) alpha binding. We describe the biodistribution and tumor accumulation of (89)Zr-labeled CEA-IL2v. Twenty-four patients with advanced solid CEA positive (CEA+) or negative (CEA-) tumors received CEA-IL2v 6 mg (4 CEA+; 3 CEA-), 20 mg (9 CEA+), or 30 mg (4 CEA+; 4 CEA-) biweekly. In cycle 1, 2 mg of the total dose comprised (89)Zr-CEA-IL2v (50 MBq) and serial (89)Zr-PET imaging was conducted. Four CEA+ patients with visually confirmed (89)Zr-CEA-IL2v tumor accumulation at 20 mg had repeated (89)Zr-PET imaging during cycle 4. (89)Zr-CEA-IL2v immuno-PET demonstrated preferential drug accumulation in CEA+ tumors (%ID/mLpeak CEA- 3.6 x 10(-3) vs. CEA+ 6.7 x10(-3)). There was a non-significant trend towards dose-dependent tumor uptake, with higher uptake at doses >/=20 mg. Biodistribution was dose- and CEA-independent with major accumulation in lymphoid tissue compatible with IL-2R binding. Reduced exposure and reduced tumor accumulation (%ID/mLpeak 57% lower) on cycle 4 vs. cycle 1 was consistent with peripheral expansion of immune cells. The findings of this immune PET imaging study with (89)Zr-CEA-IL2v support the therapeutic concept of CEA-IL2v, confirming selective and targeted tumor accumulation with this novel immunocytokine.

Author Info: (1) The Netherlands Cancer Institute, Amsterdam, The Netherlands. Centre for Human Drug Research, Leiden, The Netherlands. (2) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands

Author Info: (1) The Netherlands Cancer Institute, Amsterdam, The Netherlands. Centre for Human Drug Research, Leiden, The Netherlands. (2) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands. (3) The Netherlands Cancer Institute, Amsterdam, The Netherlands. (4) Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland. (5) The Netherlands Cancer Institute, Amsterdam, The Netherlands. (6) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands. (7) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands. (8) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands. (9) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands. (10) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands. (11) Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland. (12) Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland. (13) Roche Pharma Research and Early Development, Roche Innovation Center, Zurich, Switzerland. (14) The Netherlands Cancer Institute, Amsterdam, The Netherlands. Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands. (15) VU University Medical Center/Cancer Centre, Amsterdam, The Netherlands.

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Trial Watch: Immunostimulation with recombinant cytokines for cancer therapy

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Cytokines regulate virtually aspects of innate and adaptive immunity, including the initiation, execution and extinction of tumor-targeting immune responses. Over the past three decades, the possibility of using recombinant cytokines as a means to elicit or boost clinically relevant anticancer immune responses has attracted considerable attention. However, only three cytokines have been approved so far by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, namely, recombinant interleukin (IL)-2 and two variants of recombinant interferon alpha 2 (IFN-alpha2a and IFN-alpha2b). Moreover, the use of these cytokines in the clinics is steadily decreasing, mostly as a consequence of: (1) the elevated pleiotropism of IL-2, IFN-alpha2a and IFN-alpha2b, resulting in multiple unwarranted effects; and (2) the development of highly effective immunostimulatory therapeutics, such as immune checkpoint blockers. Despite this and other obstacles, research in the field continues as alternative cytokines with restricted effects on specific cell populations are being evaluated. Here, we summarize research preclinical and clinical developments on the use of recombinant cytokines for immunostimulation in cancer patients.

Author Info: (1) Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. (2) Department of Medicine and Immunology Program, Memorial Sloan Kettering Cancer Center, New York

Author Info: (1) Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. (2) Department of Medicine and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY. (3) Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA. (4) Immunoreceptors of the Innate and Adaptive System, IDIBAPS, Barcelona, Spain. (5) Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. (6) Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. (7) Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. (8) Hematology and Oncology Department, Hospital Universitario Morales Meseguer, Murcia, Spain. (9) Sotio, Prague, Czech Republic. Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic. (10) Sotio, Prague, Czech Republic. Dept. of Immunology, 2nd Faculty of Medicine and University Hospital Motol, Charles University, Prague, Czech Republic. (11) Gustave Roussy Comprehensive Cancer Institute, Villejuif, France. INSERM, U1015, Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France. Universite Paris Sud/Paris XI, Le Kremlin-Bicetre, France. (12) Universite Paris Descartes/Paris V, France. Universite Pierre et Marie Curie/Paris VI, Paris. Equipe 11 labellisee Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. INSERM, U1138, Paris, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France. Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden. Pole de Biologie, Hopital Europeen George Pompidou, AP-HP, Paris, France. (13) Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA. Universite Paris Descartes/Paris V, France. Sandra and Edward Meyer Cancer Center, New York, NY, USA.

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Prospects of IL-2 in Cancer Immunotherapy

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IL-2 is a powerful immune growth factor and it plays important role in sustaining T cell response. The potential of IL-2 in expanding T cells without loss of functionality has led to its early use in cancer immunotherapy. IL-2 has been reported to induce complete and durable regressions in cancer patients but immune related adverse effects have been reported (irAE). The present review discusses the prospects of IL-2 in immunotherapy for cancer.

Author Info: (1) Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University

Author Info: (1) Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia. (2) Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia. (3) Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia. (4) Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia. (5) Department of Biochemistry, Cancer Metabolism and Epigenetic Unit, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia. (6) Department of Medicine, University of California, San Francisco, CA 94143, USA. (7) King Fahd Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia. Department of Molecular Genetics and Enzymology, Division of Human Genetics and Genome Research, National Research Center, Giza, Egypt. (8) Department of Biochemistry, University of Jeddah, Jeddah, Saudi Arabia. (9) Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia. (10) King Fahd Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia.

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