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Improving Immunotherapy Through Glycodesign.

Matthew J Buettner1, Sagar R Shah1, Christopher T Saeui1,2

  • 1Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, Baltimore, MD, United States.

Frontiers in Immunology
|November 20, 2018
PubMed
Summary
This summary is machine-generated.

Glycoengineering optimizes glycosylation to enhance immunotherapy safety and efficacy. This approach improves antibodies, proteins, and cell therapies, overcoming past development challenges.

Keywords:
antibody-dependent cell cytotoxicity (ADCC)antibody-drug conjugates (ADCs)glycoengineeringglycosylationimmunotherapymetabolic glycoengineeringmonoclonal antibodies

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Area of Science:

  • Biochemistry and Biotechnology
  • Immunology
  • Pharmaceutical Sciences

Background:

  • Immunotherapy represents a significant advancement in modern medicine, with many recent high-impact drugs belonging to this class.
  • Glycosylation, a critical factor influencing immunotherapeutic safety, biological activity, and pharmacokinetics, has historically presented challenges in drug development.
  • Despite successes, optimizing glycosylation remains a key hurdle for advancing immunotherapeutic treatments.

Purpose of the Study:

  • To explore the role of glycoengineering in overcoming glycosylation-related challenges in immunotherapy development.
  • To highlight how optimized glycosylation can improve the safety, efficacy, and pharmacokinetic properties of immunotherapeutics.
  • To discuss the application of glycoengineering strategies from pre-clinical development through biomanufacturing.

Main Methods:

  • Review of glycoengineering strategies for modulating protein glycosylation.
  • Analysis of design principles for optimizing glycosylation in early-stage immunotherapeutic development.
  • Examination of glycoengineering's impact on biomanufacturing processes for immunotherapeutics.

Main Results:

  • Glycoengineering offers significant opportunities to enhance immunotherapies, including antibodies, recombinant proteins, and cell-based therapies.
  • Optimized glycosylation can mitigate previous development pitfalls and improve therapeutic outcomes.
  • Glycoengineering strategies can be integrated into biomanufacturing to ensure consistent immunotherapeutic effectiveness.

Conclusions:

  • Strategic glycoengineering is crucial for advancing the development and application of novel immunotherapies.
  • Optimizing glycosylation through glycoengineering presents a pathway to improved safety, efficacy, and manufacturability of immunotherapeutics.
  • This approach holds promise for overcoming existing limitations and maximizing the potential of immunotherapy.