Biobetters pp 63-77 | Cite as

Novel Methods for Addressing Immunogenicity of Therapeutic Enzymes

  • Leslie P. Cousens
  • Leonard Moise
  • Anne S. De Groot
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 19)

Abstract

While the biotechnology revolution has contributed to the development of life-saving replacement proteins for blood factor and enzyme such as hemophilia and Pompe disease, these therapies can induce immune responses leading to treatment failure. The degree of immune response is dependent on whether the patient has established tolerance to the missing protein. For example, Pompe patients that do not produce any natural lysosomal acid alpha-glucosidase (GAA) enzyme are categorized as cross-reactive immunologic material (CRIM)-negative, and those with partial GAA protein expression, are categorized as CRIM-positive. The interdependent relationship between incidence of ADA and CRIM-status in Pompe patients leads to the following dilemma: the less GAA expressed, the more severe the disease, the greater the dependence on the replacement protein, but the greater the risk and severity of ADA. Thus, in spite of having an effective treatment for Pompe disease, there remains a critical unmet medical need for a less immunogenic GAA, especially for CRIM-negative babies. New methods for inducing tolerance to GAA have been developed in recent years, which are reviewed here. They include drug-induced tolerance, deimmunization (removal of T cell epitope triggers for immune response) and antigen-specific tolerance induction using Tregitope, a novel regulatory T-cell inducing intervention.

Keywords

Toxicity Leukemia Methotrexate Myeloma Encephalitis 

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Copyright information

© American Association of Pharmaceutical Scientists 2015

Authors and Affiliations

  • Leslie P. Cousens
    • 1
  • Leonard Moise
    • 1
    • 2
  • Anne S. De Groot
    • 1
    • 2
  1. 1.EpiVax, Inc.ProvidenceUSA
  2. 2.Institute of Immunology and InformaticsUniversity of Rhode IslandKingstonUSA

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