title: Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins.
abstract: 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.
authors: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.
authors: Alison
authors: A
authors: Smith
authors: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.
authors: Hugh
authors: H
authors: Manoli
authors: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.
authors: Stacey
authors: S
authors: Jaw
authors: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.
authors: Kimberley
authors: K
authors: Frutoz
authors: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.
authors: Alan L
authors: AL
authors: Epstein
authors: Department of Pathology, Keck School of Medicine of University of Southern California, Los Angeles, CA 90089, USA.
authors: Leslie A
authors: 0000-0002-7346-2818
authors: LA
authors: Khawli
authors: Nonclinical Development, UCB Biopharma SPRL, 1420 Braine-l'Alleud, Belgium.
authors: Frank-Peter
authors: 0000-0003-4042-6949
authors: FP
authors: Theil
mesh_terms: D000818:Animals; D001688:Biological Products / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology*; D003198:Computer Simulation; D019468:Disease Management; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000494:pharmacology; D056747:Immunomodulation; D008954:Models, Biological; D018448:Models, Immunological; D015202:Protein Engineering; D011506:Proteins / Q000009:adverse effects / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D001688:Biological Products; D007155:Immunologic Factors; D011506:Proteins