Abstract
Several monoclonal antibodies bind in a highly selective manner to tumor-associated glycoforms of MUC1. We set out to exploit this by developing a MUC1-specific chimeric antigen receptor. Difficulties were encountered in this endeavor, owing to MUC1-imposed steric hindrance and antigenic heterogeneity. These issues were addressed by the iterative engineering of all components of the fusion receptor. Our experience underlines the need for careful individual optimization of immunotherapeutic reagents as dictated by the molecular vagaries of the target under study.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Chemotaxis, Leukocyte / genetics*
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Chemotaxis, Leukocyte / immunology
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Gene Transfer Techniques
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Genetic Therapy / methods
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Humans
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Immunotherapy / methods*
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Models, Biological
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Mucin-1 / metabolism*
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Neoplasms / genetics
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Neoplasms / immunology
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Neoplasms / metabolism
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Neoplasms / therapy*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Antigen, T-Cell / physiology*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology*
Substances
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Mucin-1
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Receptors, Antigen, T-Cell
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Recombinant Fusion Proteins