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Monoclonal antibodies: technologies for early discovery and engineering

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      Most cited references 147

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      Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

      Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P=0.006). Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).
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        Continuous cultures of fused cells secreting antibody of predefined specificity.

         G Köhler,  C Milstein (1975)
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          A new initiative on precision medicine.

          President Obama has announced a research initiative that aims to accelerate progress toward a new era of precision medicine, with a near-term focus on cancers and a longer-term aim to generate knowledge applicable to the whole range of health and disease.
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            Author and article information

            Affiliations
            [1 ] i3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal;
            [2 ] INEB – Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal;
            [3 ] IPATIMUP – Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal;
            [4 ] ICBAS – Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal;
            [5 ] Departmento de Engenharia Metalúrgica e de Materiais, FEUP – Faculdade de Engenharia da Universidade do Porto, Porto, Portugal;
            [6 ] CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde & Instituto Universitário de Ciências da Saúde, Gandra, Portugal
            Journal
            Critical Reviews in Biotechnology
            Critical Reviews in Biotechnology
            Informa UK Limited
            0738-8551
            1549-7801
            August 08 2017
            April 03 2018
            August 08 2017
            April 03 2018
            : 38
            : 3
            : 394-408
            10.1080/07388551.2017.1357002
            © 2018

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