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      Utilizing Immunocytokines for Cancer Therapy

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          Abstract

          Cytokine therapy for cancer has indicated efficacy in certain diseases but is generally accompanied by severe toxicity. The field of antibody–cytokine fusion proteins (immunocytokines) arose to target these effector molecules to the tumor environment in order to expand the therapeutic window of cytokine therapy. Pre-clinical evidence has shown the increased efficacy and decreased toxicity of various immunocytokines when compared to their cognate unconjugated cytokine. These anti-tumor properties are markedly enhanced when combined with other treatments such as chemotherapy, radiotherapy, and checkpoint inhibitor antibodies. Clinical trials that have continued to explore the potential of these biologics for cancer therapy have been conducted. This review covers the in vitro, in vivo, and clinical evidence for the application of immunocytokines in immuno-oncology.

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          Cancer immunoediting: from immunosurveillance to tumor escape.

          The concept that the immune system can recognize and destroy nascent transformed cells was originally embodied in the cancer immunosurveillance hypothesis of Burnet and Thomas. This hypothesis was abandoned shortly afterwards because of the absence of strong experimental evidence supporting the concept. New data, however, clearly show the existence of cancer immunosurveillance and also indicate that it may function as a component of a more general process of cancer immunoediting. This process is responsible for both eliminating tumors and sculpting the immunogenic phenotypes of tumors that eventually form in immunocompetent hosts. In this review, we will summarize the historical and experimental basis of cancer immunoediting and discuss its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction.
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            Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

            Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)
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              Continuous cultures of fused cells secreting antibody of predefined specificity.

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                Author and article information

                Journal
                Antibodies (Basel)
                Antibodies (Basel)
                antibodies
                Antibodies
                MDPI
                2073-4468
                09 March 2021
                March 2021
                : 10
                : 1
                : 10
                Affiliations
                [1 ]ImmunoEngineering Group, School of Cancer and Pharmaceutical Studies, King’s College London, London SE19RT, UK; runbecke@ 123456email.chop.edu
                [2 ]St. John’s Institute of Dermatology, School of Basic and Medical Biosciences, King’s College London, London SE1 9RT, UK; silvia.crescioli@ 123456kcl.ac.uk (S.C.); sophia.karagiannis@ 123456kcl.ac.uk (S.N.K.)
                Author notes
                [* ]Correspondence: sophie.papa@ 123456kcl.ac.uk
                Author information
                https://orcid.org/0000-0002-1909-5957
                https://orcid.org/0000-0002-4100-7810
                https://orcid.org/0000-0002-9063-7675
                Article
                antibodies-10-00010
                10.3390/antib10010010
                8006145
                33803078
                a0f4060f-91f1-4321-8c9a-ff156c3bb8b2
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 January 2021
                : 22 February 2021
                Categories
                Review

                antibody,antibody engineering,immunocytokine,immunotherapy,cytokines,cancer therapy

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