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Emerging approaches to induce immune tolerance to therapeutic proteins

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TRENDS IN PHARMACOLOGICAL SCIENCES
卷 44, 期 12, 页码 1028-1042

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CELL PRESS
DOI: 10.1016/j.tips.2023.10.002

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Immunological tolerance is crucial in addressing the immunogenicity of therapeutic proteins. Traditional approaches are inefficient and expensive, but recent studies have shown promising results with emerging technologies. Overcoming barriers is still necessary for translation into the clinic.
Immunogenicity affects the safety and efficacy of therapeutic proteins. This review is focused on approaches for inducing immunological tolerance to circumvent the immunogenicity of therapeutic proteins in the clinic. The few immune tolerance strategies that are used in the clinic tend to be inefficient and expensive and typically involve global immunosuppression, putting patients at risk of infections. The hallmark of a desirable immune tolerance regimen is the specific alleviation of immune responses to the therapeutic protein. In the past decade, proof-of-principle studies have demonstrated that emerging technologies, including nanoparticle-based delivery of immunomodulators, cellular targeting and depletion, cellular engineering, gene therapy, and gene editing, can be leveraged to promote tolerance to therapeutic proteins. We discuss the potential of these novel approaches and the barriers that need to be overcome for translation into the clinic.

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