title: Considerations for optimization and validation of an in vitro PBMC derived T cell assay for immunogenicity prediction of biotherapeutics.
abstract: An immune response to a biotherapeutic can be induced when the therapeutic is processed and presented by antigen presenting cell to T helper cells. This study evaluates the performance of an in vitro assay that can elicit antigen specific effector T cell responses. Two biotherapeutics with known clinical immunogenicity [FPX1 and FPX2] were assessed for their ability to induce antigen-specific IFN-γ secreting T cells in peripheral blood mononuclear cells (PBMC). The 24 amino acid peptide component of FPX1 elicited an antigen-specific response in 16/34 (47%) individual naïve healthy donors. This in vitro effect was consistent with high rate of immunogenicity which was observed when this drug was administered in clinical trials. FPX2 did not induce antigen-specific T cells in vitro, which correlates with the low rate of development of anti-drug antibody responses to this molecule in the clinic. The assay has the potential to predict immunogenicity and help in the selection of biotherapeutics at the early development stage of a clinical candidate.
authors: Medical Sciences (Clinical Immunology and Biostatistics), Amgen, Thousand Oaks, CA, USA.
authors: Danika
authors: D
authors: Wullner
authors: Lei
authors: L
authors: Zhou
authors: Erica
authors: E
authors: Bramhall
authors: Andrew
authors: A
authors: Kuck
authors: Theresa J
authors: TJ
authors: Goletz
authors: Steven
authors: S
authors: Swanson
authors: Narendra
authors: N
authors: Chirmule
authors: Vibha
authors: V
authors: Jawa
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D001691:Biological Therapy / Q000009:adverse effects*; D018929:Cell Culture Techniques; D002470:Cell Survival; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology* / Q000627:therapeutic use; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D007141:Immunoglobulin Fc Fragments; D010446:Peptide Fragments; D010455:Peptides; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D007371:Interferon-gamma