[PubMed] [Google Scholar] [76] Assier E, Jullien V, Lefort J, Moreau JL, Vargaftig BB, Jose Lapa JLE, Thze J, Cytokine 2005, 32, 280. review provides a brief background around the characteristics of cytokines and their history as clinical therapeutics, followed by a deeper discussion around the UK 5099 engineering strategies developed UK 5099 for cytokine therapies with a focus on the translational relevance of these approaches. comes from the Greek word meaning heat and meaning generating).[41] By the 1970s and 80s, interest in therapeutic applications in cytokines increased as more cytokines were identified and the generation of recombinant proteins became possible.[29] During this time, interferon was found to have many other effects beyond preventing viral infection such as enhancement of cell function, immune system modulation, and inhibition of cell division with antitumor activity immunomodulation. healthy subjects, autoimmune hepatitis || bipolar disorder/unipolar depressive disorder/cognitive impairment, mantle cell lymphoma, premature infant, asthma, amyotrophic lateral sclerosis, eosinophilia/angioedema || anemia, chronic kidney disease, erythroblastosis fetalis, hypoxic-ischemic encephalopathy, intraventricular hemorrhage of prematurity, traumatic optic neuropathy, myelodysplastic syndromesG-CSF24 (3)28 (3)97 (19)51 (14) 200 Indic.solid tumor/ NSCLC/SCLC, advanced pancreatic cancer, postmenopausal symptoms || neurological diseases, multiple myeloma, lymphoma/leukemia, Fanconi anemia, early stage BC, Crohns disease, heart failure || squamous cell carcinoma of the oral cavity, neuroblastoma, glioblastoma/gliosarcoma, recurrent neuroblastoma, colon cancer || pulmonary alveolar proteinosisIFNa)15 (4)9 (1)59 (7)29 (1) 112 Indic.various tumor malignancies || renal cell carcinoma/melanoma, lymphomatoid granulomatosis, chronic myeloid leukemia, breast cancer || malignant pleural mesotheliomaIFN-45 (9)82 (6)360 (20)259 (11) 746 Indic.Triple-negative BC || adverse effects of immunotherapy, squamous cell carcinoma, prostate cancer, recurrent ovarian cancer, myeloproliferative disorders, metastatic liver carcinoma, lymphoma, leukemia || polycythemia vera, melanoma, chronic myeloid leukemia, hepatitis, COVID-19IFN-430 (5)40 (3)49 (12) 123 Indic.solid tumor/NSCLC/SCLC, malignant solid tumors, endometrial clear cell adenocarcinoma, stage III melanoma, hepatocellular carcinoma || relapsing/remitting multiple sclerosis, COVID-19, MERS-CoVIFN-8 (1)16 (1)40 (1)15 79 Indic.ovarian cancer || breast cancerIFN-17 (2)7 15 Indic.hepatitis D, COVID-19IL-1412 7 IL-102111 5 IL-11183 (1) 12 Indic.nasopharyngeal carcinomaIL-12451 (5)24 (1) 79 Indic.HIV, malignant epithelial tumors, sound tumors, acute myeloid leukemia || TNBCIL-131 1 IL-1511 (4)2 13 Indic.Relapsed T cell lymphoma, peripheral T cell lymphoma, UK 5099 metastatic solid tumors, leukemiaIL-1811 2 IL-216 (1)95 (25)233 (62)27 (4) 371 Indic.ulcerative colitis, allotransplantation, solid tumors, recurrent or platinum resistant OC, metastatic colorectal carcinoma || type 1 diabetes, systemic lupus erythematosus, stage IV gastric carcinoma/stage IV nasopharyngeal carcinoma/lymphomas, autoimmune diseases, relapsing polychondritis, recurrent miscarriage, recurrent melanoma, recurrent acute myeloid leukemia, polymyalgia rheumatica, pleural mesothelioma, pemphigus vulgaris, NSCLC, metastatic OC, liver transplant, HIV, inflammatory myopathy, head UK 5099 and neck tumors, Crohns disease, chronic graft versus host disease, bone sarcoma, Behcets disease, amyotrophic lateral sclerosis, advanced plural mesothelioma, acute coronary syndromes || acute myeloid leukemia || and in clinicaltrials.gov. Only interventional studies were included. Studies including the terms or were excluded. a)IFN type not specified in the intervention category for the clinical trial registry Classification of early phase 1 as phase 1, phase1|phase2 as phase 2 and phase2|phase3 as phase 3 A total of 145 clinical trials used a combination of cytokines Acronyms: BC C breast malignancy; OC C ovarian cancer; TNBC C triple-negative breast malignancy; NSCLC C non-small-cell lung carcinoma; SCLC C small cell lung cancer; HIV C human immunodeficiency computer virus; MERS-CoV C middle east respiratory syndrome coronavirus; COVID-19 C coronavirus disease 19 From Table 2, the major targeted indications for cytokine-based therapies continue to be malignancy (~35%) and infections (~20%) with autoimmune conditions as the third most common class (~8%). Importantly, the use of cytokines in cancer has received renewed interest due to the success of checkpoint inhibitors (CPIs)[57]. The success of CPI treatment is usually highly dependent on immune infiltration of the tumor, which could be modulated via cytokine administration prior to or in combination with CPIs.[58] Combination treatments of highly immunostimulatory cytokines and CPIs are one of the main drivers for the recent increase in IL-2 clinical trials (indicated by the high fraction of active trials in Table 2). Furthermore, as will be noted in examples provided in this review, cytokine-based combination therapies also have therapeutic potential with radiotherapy, chemotherapy, cancer vaccines, and cellular therapies. [57,58] In addition to the three major indication classes pointed out, there are many other potential applications for cytokine therapies. This is exhibited by the various non-cancer indications in active clinical trials shown in Table 2 such as neurological STMN1 diseases, inflammatory diseases, fibrotic disease, and wound healing.[59] 4.?Clinical Perspective The basis for using cytokine therapies in the clinic is usually understanding their mechanism of action and toxicities. Many of.

[PubMed] [Google Scholar] [76] Assier E, Jullien V, Lefort J, Moreau JL, Vargaftig BB, Jose Lapa JLE, Thze J, Cytokine 2005, 32, 280