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Antibodies (Basel) ; 10(4)2021 Nov 04.
Article in English | MEDLINE | ID: covidwho-1595331


Monoclonal antibodies (mAbs) are one of the cornerstones of modern medicine, across an increasing range of therapeutic areas. All therapeutic mAbs are glycoproteins, i.e., their polypeptide chain is decorated with glycans, oligosaccharides of extraordinary structural diversity. The presence, absence, and composition of these glycans can have a profound effect on the pharmacodynamic and pharmacokinetic profile of individual mAbs. Approaches for the glycoengineering of therapeutic mAbs-the manipulation and optimisation of mAb glycan structures-are therefore of great interest from a technological, therapeutic, and regulatory perspective. In this review, we provide a brief introduction to the effects of glycosylation on the biological and pharmacological functions of the five classes of immunoglobulins (IgG, IgE, IgA, IgM and IgD) that form the backbone of all current clinical and experimental mAbs, including an overview of common mAb expression systems. We review selected examples for the use of small molecule inhibitors of glycan biosynthesis for mAb glycoengineering, we discuss the potential advantages and challenges of this approach, and we outline potential future applications. The main aim of the review is to showcase the expanding chemical toolbox that is becoming available for mAb glycoengineering to the biology and biotechnology community.

Cancer Cell ; 39(2): 257-275.e6, 2021 02 08.
Article in English | MEDLINE | ID: covidwho-1009339


Given the immune system's importance for cancer surveillance and treatment, we have investigated how it may be affected by SARS-CoV-2 infection of cancer patients. Across some heterogeneity in tumor type, stage, and treatment, virus-exposed solid cancer patients display a dominant impact of SARS-CoV-2, apparent from the resemblance of their immune signatures to those for COVID-19+ non-cancer patients. This is not the case for hematological malignancies, with virus-exposed patients collectively displaying heterogeneous humoral responses, an exhausted T cell phenotype and a high prevalence of prolonged virus shedding. Furthermore, while recovered solid cancer patients' immunophenotypes resemble those of non-virus-exposed cancer patients, recovered hematological cancer patients display distinct, lingering immunological legacies. Thus, while solid cancer patients, including those with advanced disease, seem no more at risk of SARS-CoV-2-associated immune dysregulation than the general population, hematological cancer patients show complex immunological consequences of SARS-CoV-2 exposure that might usefully inform their care.

COVID-19/immunology , Neoplasms/immunology , Neoplasms/virology , Severe Acute Respiratory Syndrome/immunology , Adult , Aged , Aged, 80 and over , COVID-19/etiology , COVID-19/mortality , Female , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Hematologic Neoplasms/virology , Humans , Immunophenotyping , Male , Middle Aged , Nasopharynx/virology , Neoplasms/mortality , Neoplasms/therapy , Severe Acute Respiratory Syndrome/etiology , Severe Acute Respiratory Syndrome/mortality , Severe Acute Respiratory Syndrome/virology , T-Lymphocytes/virology , Virus Shedding , Young Adult