A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice
Abstract Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is...
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| Format: | Article |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53839-5 |
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| author | Aman Mebrahtu Ida Laurén Rosanne Veerman Gözde Güclüler Akpinar Martin Lord Alexandros Kostakis Juan Astorga-Wells Leif Dahllund Anders Olsson Oscar Andersson Jonathan Persson Helena Persson Pierre Dönnes Johan Rockberg Sara Mangsbo |
| author_facet | Aman Mebrahtu Ida Laurén Rosanne Veerman Gözde Güclüler Akpinar Martin Lord Alexandros Kostakis Juan Astorga-Wells Leif Dahllund Anders Olsson Oscar Andersson Jonathan Persson Helena Persson Pierre Dönnes Johan Rockberg Sara Mangsbo |
| author_sort | Aman Mebrahtu |
| collection | DOAJ |
| description | Abstract Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is designed to facilitate peptide antigen delivery to CD40 expressing cells combined with simultaneous CD40 agonistic activity. In vivo, the selected bispecific antibody BiA9*2_HF loaded with peptide cargos induces improved antigen-specific proliferation of CD8+ (10-15 fold) and CD4+ T cells (2-7 fold) over control in draining lymph nodes. In both virus-induced and neoantigen-based mouse tumor models, BiA9*2_HF demonstrates therapeutic efficacy and elevated safety profile, with complete tumor clearance, as well as measured abscopal impact on tumor growth. The BiA9*2_HF drug candidate can thus be utilized to tailor immunotherapeutics for cancer patients. |
| format | Article |
| id | doaj-art-d469af897715422a9a5f977bb3bd08a2 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d469af897715422a9a5f977bb3bd08a22024-11-17T12:37:45ZengNature PortfolioNature Communications2041-17232024-11-0115112010.1038/s41467-024-53839-5A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in miceAman Mebrahtu0Ida Laurén1Rosanne Veerman2Gözde Güclüler Akpinar3Martin Lord4Alexandros Kostakis5Juan Astorga-Wells6Leif Dahllund7Anders Olsson8Oscar Andersson9Jonathan Persson10Helena Persson11Pierre Dönnes12Johan Rockberg13Sara Mangsbo14KTH Royal Institute of Technology, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and HealthStrike Pharma ABStrike Pharma ABStrike Pharma ABStrike Pharma ABStrike Pharma ABDepartment of Medical Biochemistry and Biophysics, Karolinska InstituteKTH Royal Institute of Technology, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and HealthKTH Royal Institute of Technology, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and HealthKTH Royal Institute of Technology, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and HealthKTH Royal Institute of Technology, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and HealthKTH Royal Institute of Technology, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and HealthStrike Pharma ABKTH Royal Institute of Technology, Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and HealthStrike Pharma ABAbstract Current antibody-based immunotherapy depends on tumor antigen shedding for proper T cell priming. Here we select a novel human CD40 agonistic drug candidate and generate a bispecific antibody, herein named BiA9*2_HF, that allows for rapid antibody-peptide conjugate formation. The format is designed to facilitate peptide antigen delivery to CD40 expressing cells combined with simultaneous CD40 agonistic activity. In vivo, the selected bispecific antibody BiA9*2_HF loaded with peptide cargos induces improved antigen-specific proliferation of CD8+ (10-15 fold) and CD4+ T cells (2-7 fold) over control in draining lymph nodes. In both virus-induced and neoantigen-based mouse tumor models, BiA9*2_HF demonstrates therapeutic efficacy and elevated safety profile, with complete tumor clearance, as well as measured abscopal impact on tumor growth. The BiA9*2_HF drug candidate can thus be utilized to tailor immunotherapeutics for cancer patients.https://doi.org/10.1038/s41467-024-53839-5 |
| spellingShingle | Aman Mebrahtu Ida Laurén Rosanne Veerman Gözde Güclüler Akpinar Martin Lord Alexandros Kostakis Juan Astorga-Wells Leif Dahllund Anders Olsson Oscar Andersson Jonathan Persson Helena Persson Pierre Dönnes Johan Rockberg Sara Mangsbo A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice Nature Communications |
| title | A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice |
| title_full | A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice |
| title_fullStr | A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice |
| title_full_unstemmed | A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice |
| title_short | A bispecific CD40 agonistic antibody allowing for antibody-peptide conjugate formation to enable cancer-specific peptide delivery, resulting in improved T Cell proliferation and anti-tumor immunity in mice |
| title_sort | bispecific cd40 agonistic antibody allowing for antibody peptide conjugate formation to enable cancer specific peptide delivery resulting in improved t cell proliferation and anti tumor immunity in mice |
| url | https://doi.org/10.1038/s41467-024-53839-5 |
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