Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics

Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target ‘foreign’ sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xenosequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics ‘quality by design’, may lead to the development of ever more clinically effective, but less immunogenic, biologics

Data for: Increase in asthma prevalence in adults in temporary housing after the Great East Japan Earthquake

Background: It is unknown whether disasters such as earthquakes and tsunamis affect asthma development or exacerbation in the elderly. Here, we investigated whether asthma prevalence increased in the elderly living in temporary housing after the Great East Japan Earthquake.Methods: We diagnosed asthma according to GINA guidelines in residents 15 years or older who were living, or had lived, in temporary housing in the city of Ishinomaki. We analyzed serum antigen-specific anti-immunoglobulin E (IgE) antibody levels to Dermatophagoides farinae (Der f), Aspergillus fumigatus, Aspergillus glaucus, Aspergillus amstelodami, and Aspergillus restrictus.Results: The average age of the 337 inhabitants was 61.3 ± 15.8 years (men, 37.7% ). The asthma prevalence was 24.9% by specialist diagnosis. The antigen-specific IgE antibody titer against Der f, but none of the other test antigens, was significantly higher in the asthma group than in the no-asthma group (P < 0.01). Time of asthma onset was before the earthquake, 44.6%; in shelters, 9.5%, and after moving into temporary housing, 45.9%. In 71.4% of asthmatics there was exacerbation of asthma after temporary housing occupancy. Logistic regression revealed that the risk factors for developing asthma after moving into temporary housing were more middle-aged (P < 0.05), allergic rhinitis or allergic conjunctivitis (P < 0.05), family asthma history (P < 0.05), never having smoked (P < 0.01), and peripheral airways disorder (lower % V50) (P < 0.05), but not depression.Conclusions: The earthquake and tsunami disasters increased mite allergen sensitization and exacerbation or development of asthma in elderly residents.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Increase in asthma prevalence in adults in temporary housing after the Great East Japan Earthquake

Background: It is unknown whether disasters such as earthquakes and tsunamis affect asthma development or exacerbation in the elderly. Here, we investigated whether asthma prevalence increased in the elderly living in temporary housing after the Great East Japan Earthquake.Methods: We diagnosed asthma according to GINA guidelines in residents 15 years or older who were living, or had lived, in temporary housing in the city of Ishinomaki. We analyzed serum antigen-specific anti-immunoglobulin E (IgE) antibody levels to Dermatophagoides farinae (Der f), Aspergillus fumigatus, Aspergillus glaucus, Aspergillus amstelodami, and Aspergillus restrictus.Results: The average age of the 337 inhabitants was 61.3 ± 15.8 years (men, 37.7% ). The asthma prevalence was 24.9% by specialist diagnosis. The antigen-specific IgE antibody titer against Der f, but none of the other test antigens, was significantly higher in the asthma group than in the no-asthma group (P < 0.01). Time of asthma onset was before the earthquake, 44.6%; in shelters, 9.5%, and after moving into temporary housing, 45.9%. In 71.4% of asthmatics there was exacerbation of asthma after temporary housing occupancy. Logistic regression revealed that the risk factors for developing asthma after moving into temporary housing were more middle-aged (P < 0.05), allergic rhinitis or allergic conjunctivitis (P < 0.05), family asthma history (P < 0.05), never having smoked (P < 0.01), and peripheral airways disorder (lower % V50) (P < 0.05), but not depression.Conclusions: The earthquake and tsunami disasters increased mite allergen sensitization and exacerbation or development of asthma in elderly residents.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Increase in asthma prevalence in adults in temporary housing after the Great East Japan Earthquake

Background: It is unknown whether disasters such as earthquakes and tsunamis affect asthma development or exacerbation in the elderly. Here, we investigated whether asthma prevalence increased in the elderly living in temporary housing after the Great East Japan Earthquake.Methods: We diagnosed asthma according to GINA guidelines in residents 15 years or older who were living, or had lived, in temporary housing in the city of Ishinomaki. We analyzed serum antigen-specific anti-immunoglobulin E (IgE) antibody levels to Dermatophagoides farinae (Der f), Aspergillus fumigatus, Aspergillus glaucus, Aspergillus amstelodami, and Aspergillus restrictus.Results: The average age of the 337 inhabitants was 61.3 ± 15.8 years (men, 37.7% ). The asthma prevalence was 24.9% by specialist diagnosis. The antigen-specific IgE antibody titer against Der f, but none of the other test antigens, was significantly higher in the asthma group than in the no-asthma group (P < 0.01). Time of asthma onset was before the earthquake, 44.6%; in shelters, 9.5%, and after moving into temporary housing, 45.9%. In 71.4% of asthmatics there was exacerbation of asthma after temporary housing occupancy. Logistic regression revealed that the risk factors for developing asthma after moving into temporary housing were more middle-aged (P < 0.05), allergic rhinitis or allergic conjunctivitis (P < 0.05), family asthma history (P < 0.05), never having smoked (P < 0.01), and peripheral airways disorder (lower % V50) (P < 0.05), but not depression.Conclusions: The earthquake and tsunami disasters increased mite allergen sensitization and exacerbation or development of asthma in elderly residents.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Increase in asthma prevalence in adults in temporary housing after the Great East Japan Earthquake

Background: It is unknown whether disasters such as earthquakes and tsunamis affect asthma development or exacerbation in the elderly. Here, we investigated whether asthma prevalence increased in the elderly living in temporary housing after the Great East Japan Earthquake.Methods: We diagnosed asthma according to GINA guidelines in residents 15 years or older who were living, or had lived, in temporary housing in the city of Ishinomaki. We analyzed serum antigen-specific anti-immunoglobulin E (IgE) antibody levels to Dermatophagoides farinae (Der f), Aspergillus fumigatus, Aspergillus glaucus, Aspergillus amstelodami, and Aspergillus restrictus.Results: The average age of the 337 inhabitants was 61.3 ± 15.8 years (men, 37.7% ). The asthma prevalence was 24.9% by specialist diagnosis. The antigen-specific IgE antibody titer against Der f, but none of the other test antigens, was significantly higher in the asthma group than in the no-asthma group (P < 0.01). Time of asthma onset was before the earthquake, 44.6%; in shelters, 9.5%, and after moving into temporary housing, 45.9%. In 71.4% of asthmatics there was exacerbation of asthma after temporary housing occupancy. Logistic regression revealed that the risk factors for developing asthma after moving into temporary housing were more middle-aged (P < 0.05), allergic rhinitis or allergic conjunctivitis (P < 0.05), family asthma history (P < 0.05), never having smoked (P < 0.01), and peripheral airways disorder (lower % V50) (P < 0.05), but not depression.Conclusions: The earthquake and tsunami disasters increased mite allergen sensitization and exacerbation or development of asthma in elderly residents.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Increase in asthma prevalence in adults in temporary housing after the Great East Japan Earthquake

Background: It is unknown whether disasters such as earthquakes and tsunamis affect asthma development or exacerbation in the elderly. Here, we investigated whether asthma prevalence increased in the elderly living in temporary housing after the Great East Japan Earthquake.Methods: We diagnosed asthma according to GINA guidelines in residents 15 years or older who were living, or had lived, in temporary housing in the city of Ishinomaki. We analyzed serum antigen-specific anti-immunoglobulin E (IgE) antibody levels to Dermatophagoides farinae (Der f), Aspergillus fumigatus, Aspergillus glaucus, Aspergillus amstelodami, and Aspergillus restrictus.Results: The average age of the 337 inhabitants was 61.3 ± 15.8 years (men, 37.7% ). The asthma prevalence was 24.9% by specialist diagnosis. The antigen-specific IgE antibody titer against Der f, but none of the other test antigens, was significantly higher in the asthma group than in the no-asthma group (P < 0.01). Time of asthma onset was before the earthquake, 44.6%; in shelters, 9.5%, and after moving into temporary housing, 45.9%. In 71.4% of asthmatics there was exacerbation of asthma after temporary housing occupancy. Logistic regression revealed that the risk factors for developing asthma after moving into temporary housing were more middle-aged (P < 0.05), allergic rhinitis or allergic conjunctivitis (P < 0.05), family asthma history (P < 0.05), never having smoked (P < 0.01), and peripheral airways disorder (lower % V50) (P < 0.05), but not depression.Conclusions: The earthquake and tsunami disasters increased mite allergen sensitization and exacerbation or development of asthma in elderly residents.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Increase in asthma prevalence in adults in temporary housing after the Great East Japan Earthquake

Background: It is unknown whether disasters such as earthquakes and tsunamis affect asthma development or exacerbation in the elderly. Here, we investigated whether asthma prevalence increased in the elderly living in temporary housing after the Great East Japan Earthquake.Methods: We diagnosed asthma according to GINA guidelines in residents 15 years or older who were living, or had lived, in temporary housing in the city of Ishinomaki. We analyzed serum antigen-specific anti-immunoglobulin E (IgE) antibody levels to Dermatophagoides farinae (Der f), Aspergillus fumigatus, Aspergillus glaucus, Aspergillus amstelodami, and Aspergillus restrictus.Results: The average age of the 337 inhabitants was 61.3 ± 15.8 years (men, 37.7% ). The asthma prevalence was 24.9% by specialist diagnosis. The antigen-specific IgE antibody titer against Der f, but none of the other test antigens, was significantly higher in the asthma group than in the no-asthma group (P < 0.01). Time of asthma onset was before the earthquake, 44.6%; in shelters, 9.5%, and after moving into temporary housing, 45.9%. In 71.4% of asthmatics there was exacerbation of asthma after temporary housing occupancy. Logistic regression revealed that the risk factors for developing asthma after moving into temporary housing were more middle-aged (P < 0.05), allergic rhinitis or allergic conjunctivitis (P < 0.05), family asthma history (P < 0.05), never having smoked (P < 0.01), and peripheral airways disorder (lower % V50) (P < 0.05), but not depression.Conclusions: The earthquake and tsunami disasters increased mite allergen sensitization and exacerbation or development of asthma in elderly residents.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Data for: Increase in asthma prevalence in adults in temporary housing after the Great East Japan Earthquake

Background: It is unknown whether disasters such as earthquakes and tsunamis affect asthma development or exacerbation in the elderly. Here, we investigated whether asthma prevalence increased in the elderly living in temporary housing after the Great East Japan Earthquake.Methods: We diagnosed asthma according to GINA guidelines in residents 15 years or older who were living, or had lived, in temporary housing in the city of Ishinomaki. We analyzed serum antigen-specific anti-immunoglobulin E (IgE) antibody levels to Dermatophagoides farinae (Der f), Aspergillus fumigatus, Aspergillus glaucus, Aspergillus amstelodami, and Aspergillus restrictus.Results: The average age of the 337 inhabitants was 61.3 ± 15.8 years (men, 37.7% ). The asthma prevalence was 24.9% by specialist diagnosis. The antigen-specific IgE antibody titer against Der f, but none of the other test antigens, was significantly higher in the asthma group than in the no-asthma group (P < 0.01). Time of asthma onset was before the earthquake, 44.6%; in shelters, 9.5%, and after moving into temporary housing, 45.9%. In 71.4% of asthmatics there was exacerbation of asthma after temporary housing occupancy. Logistic regression revealed that the risk factors for developing asthma after moving into temporary housing were more middle-aged (P < 0.05), allergic rhinitis or allergic conjunctivitis (P < 0.05), family asthma history (P < 0.05), never having smoked (P < 0.01), and peripheral airways disorder (lower % V50) (P < 0.05), but not depression.Conclusions: The earthquake and tsunami disasters increased mite allergen sensitization and exacerbation or development of asthma in elderly residents.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV