Jones Tim
Harvard University
32Publications
596Citations
Publications 8
Newest
#1Carl I. Webster (MedImmune)H-Index: 19
Last. Matthew BakerH-Index: 18
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ABSTRACTThe immunogenicity of clinically administered antibodies has clinical implications for the patients receiving them, ranging from mild consequences, such as increased clearance of the drug from the circulation, to life-threatening effects. The emergence of methods to engineer variable regions resulting in the generation of humanised and fully human antibodies as therapeutics has reduced the potential for adverse immunogenicity. However, due to differences in sequence referred to as alloty...
8 CitationsSource
#1Tim JonesH-Index: 8
Last. Matthew BakerH-Index: 18
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An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a –mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclona...
41 CitationsSource
#2Richard WeldonH-Index: 5
Last. Matthew BakerH-Index: 18
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Anti-CD52 therapy has been shown to be effective in the treatment of a number of B cell malignancies, hematopoietic disorders and autoimmune diseases (including rheumatoid arthritis and multiple sclerosis); however the current standard of treatment, the humanized monoclonal antibody alemtuzumab, is associated with the development of anti-drug antibodies in a high proportion of patients. In order to address this problem, we have identified a novel murine anti-CD52 antibody which has been humanize...
23 CitationsSource
Last. Matthew BakerH-Index: 18
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Most protein therapeutics have the potential to induce undesirable immune responses in patients. Many patients develop anti-therapeutic antibodies, which can affect the safety and efficacy of the therapeutic protein, particularly if the response is neutralizing. There are a variety of factors that influence the immunogenicity of protein therapeutics and, in particular, the presence of B- and T-cell epitopes is considered to be of importance. In silico tools to identify the location of both B- an...
124 CitationsSource
#1Tim JonesH-Index: 8
Last. Matthew BakerH-Index: 18
view all 4 authors...
Abstract Immunogenicity is a major limitation to therapy with certain monoclonal antibodies and proteins. A major driver for immunogenicity is the presence of human T-cell epitopes within the protein sequence which can activate helper T-cells resulting in the sustained production of antibodies and neutralization of the therapeutic effect. Deimmunization is a new technology for location and removal of T-cell epitopes through the combined use of immunological and molecular biology techniques. In t...
68 CitationsSource
Clinical studies show that immunogenicity observed against therapeutic proteins can limit efficacy and reduce the safety of the treatment. It is therefore beneficial to be able to predict the immunogenicity of therapeutic proteins before they enter the clinic. Studies using deimmunized proteins have highlighted the importance of T-cell epitopes in the generation of undesirable immunogenicity. In silico, in vitro, ex vivo and in vivo methods have therefore been developed that focus on identificat...
84 CitationsSource
Abstract The development of anti-therapeutic protein immune responses in patients can be a severe complication of treatment with this class of pharmaceuticals. Antibodies generated against therapeutic proteins limit the clinical efficacy of these agents by neutralizing their biological activity and/or enhancing their clearance. An assessment of the propensity of protein therapeutics to elicit immune responses in patients is likely to become an essential part of their preclinical development. It ...
106 Citations
Interferon-α (IFN-α), in conjunction with ribavirin, is the current standard for the treatment of chronic hepatitis C virus (HCV) infection. This treatment requires frequent dosing, with a significant risk of the development of anti-IFN-α neutralizing antibodies that correlates with lack of efficacy or relapse. We have developed an IFN-α linked to the Fc region of human IgG1 for improved half-life and less frequent dosing. We have also identified, using a human T cell proliferation assay, three ...
91 CitationsSource