Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins
Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecu...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2016-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2016/2342187 |
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| _version_ | 1832566885963530240 |
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| author | Alison Smith Hugh Manoli Stacey Jaw Kimberley Frutoz Alan L. Epstein Leslie A. Khawli Frank-Peter Theil |
| author_facet | Alison Smith Hugh Manoli Stacey Jaw Kimberley Frutoz Alan L. Epstein Leslie A. Khawli Frank-Peter Theil |
| author_sort | Alison Smith |
| collection | DOAJ |
| description | Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents. |
| format | Article |
| id | doaj-art-3764bc4d72d3423f8b7bbcc1f038b06d |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-3764bc4d72d3423f8b7bbcc1f038b06d2025-02-03T01:02:55ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/23421872342187Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic ProteinsAlison Smith0Hugh Manoli1Stacey Jaw2Kimberley Frutoz3Alan L. Epstein4Leslie A. Khawli5Frank-Peter Theil6Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USADepartment of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USADepartment of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USADepartment of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USADepartment of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USADepartment of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USANonclinical Development, UCB Biopharma SPRL, 1420 Braine-l’Alleud, BelgiumBiologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents.http://dx.doi.org/10.1155/2016/2342187 |
| spellingShingle | Alison Smith Hugh Manoli Stacey Jaw Kimberley Frutoz Alan L. Epstein Leslie A. Khawli Frank-Peter Theil Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins Journal of Immunology Research |
| title | Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins |
| title_full | Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins |
| title_fullStr | Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins |
| title_full_unstemmed | Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins |
| title_short | Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins |
| title_sort | unraveling the effect of immunogenicity on the pk pd efficacy and safety of therapeutic proteins |
| url | http://dx.doi.org/10.1155/2016/2342187 |
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