T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors
Abstract CD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles in solid tumors is the lack of sufficient T-cell infiltrate. Here, we show that pre-treatment vaccinat...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44308-6 |
| _version_ | 1797363042804039680 |
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| author | Jim Middelburg Marjolein Sluijter Gaby Schaap Büşra Göynük Katy Lloyd Vitalijs Ovcinnikovs Gijs G. Zom Renoud J. Marijnissen Christianne Groeneveldt Lisa Griffioen Gerwin G. W. Sandker Sandra Heskamp Sjoerd H. van der Burg Tsolere Arakelian Ferry Ossendorp Ramon Arens Janine Schuurman Kristel Kemper Thorbald van Hall |
| author_facet | Jim Middelburg Marjolein Sluijter Gaby Schaap Büşra Göynük Katy Lloyd Vitalijs Ovcinnikovs Gijs G. Zom Renoud J. Marijnissen Christianne Groeneveldt Lisa Griffioen Gerwin G. W. Sandker Sandra Heskamp Sjoerd H. van der Burg Tsolere Arakelian Ferry Ossendorp Ramon Arens Janine Schuurman Kristel Kemper Thorbald van Hall |
| author_sort | Jim Middelburg |
| collection | DOAJ |
| description | Abstract CD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles in solid tumors is the lack of sufficient T-cell infiltrate. Here, we show that pre-treatment vaccination, even when composed of tumor-unrelated antigens, induces CXCR3-mediated T-cell influx in immunologically ‘cold’ tumor models in male mice. In the absence of CD3 bsAb, the infiltrate is confined to the tumor invasive margin, whereas subsequent CD3 bsAb administration induces infiltration of activated effector CD8 T cells into the tumor cell nests. This combination therapy installs a broadly inflamed Th1-type tumor microenvironment, resulting in effective tumor eradication. Multiple vaccination formulations, including synthetic long peptides and viruses, empower CD3 bsAb therapy. Our results imply that eliciting tumor infiltration with vaccine-induced tumor-(un)related T cells can greatly improve the efficacy of CD3 bsAbs in solid tumors. |
| first_indexed | 2024-03-08T16:16:09Z |
| format | Article |
| id | doaj.art-36795cab2cda485e96053669065dc63a |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T16:16:09Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-36795cab2cda485e96053669065dc63a2024-01-07T12:35:11ZengNature PortfolioNature Communications2041-17232024-01-0115111510.1038/s41467-023-44308-6T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumorsJim Middelburg0Marjolein Sluijter1Gaby Schaap2Büşra Göynük3Katy Lloyd4Vitalijs Ovcinnikovs5Gijs G. Zom6Renoud J. Marijnissen7Christianne Groeneveldt8Lisa Griffioen9Gerwin G. W. Sandker10Sandra Heskamp11Sjoerd H. van der Burg12Tsolere Arakelian13Ferry Ossendorp14Ramon Arens15Janine Schuurman16Kristel Kemper17Thorbald van Hall18Department of Medical Oncology, Oncode Institute, Leiden University Medical CenterDepartment of Medical Oncology, Oncode Institute, Leiden University Medical CenterDepartment of Medical Oncology, Oncode Institute, Leiden University Medical CenterDepartment of Medical Oncology, Oncode Institute, Leiden University Medical CenterGenmabGenmabGenmabGenmabDepartment of Medical Oncology, Oncode Institute, Leiden University Medical CenterDepartment of Medical Oncology, Oncode Institute, Leiden University Medical CenterDepartment of Medical Imaging, Radboud Institute for Molecular Life SciencesDepartment of Medical Imaging, Radboud Institute for Molecular Life SciencesDepartment of Medical Oncology, Oncode Institute, Leiden University Medical CenterDepartment of Immunology, Leiden University Medical CenterDepartment of Immunology, Leiden University Medical CenterDepartment of Immunology, Leiden University Medical CenterGenmabGenmabDepartment of Medical Oncology, Oncode Institute, Leiden University Medical CenterAbstract CD3 bispecific antibody (CD3 bsAb) therapy is clinically approved for refractory hematological malignancies, but responses in solid tumors have been limited so far. One of the main hurdles in solid tumors is the lack of sufficient T-cell infiltrate. Here, we show that pre-treatment vaccination, even when composed of tumor-unrelated antigens, induces CXCR3-mediated T-cell influx in immunologically ‘cold’ tumor models in male mice. In the absence of CD3 bsAb, the infiltrate is confined to the tumor invasive margin, whereas subsequent CD3 bsAb administration induces infiltration of activated effector CD8 T cells into the tumor cell nests. This combination therapy installs a broadly inflamed Th1-type tumor microenvironment, resulting in effective tumor eradication. Multiple vaccination formulations, including synthetic long peptides and viruses, empower CD3 bsAb therapy. Our results imply that eliciting tumor infiltration with vaccine-induced tumor-(un)related T cells can greatly improve the efficacy of CD3 bsAbs in solid tumors.https://doi.org/10.1038/s41467-023-44308-6 |
| spellingShingle | Jim Middelburg Marjolein Sluijter Gaby Schaap Büşra Göynük Katy Lloyd Vitalijs Ovcinnikovs Gijs G. Zom Renoud J. Marijnissen Christianne Groeneveldt Lisa Griffioen Gerwin G. W. Sandker Sandra Heskamp Sjoerd H. van der Burg Tsolere Arakelian Ferry Ossendorp Ramon Arens Janine Schuurman Kristel Kemper Thorbald van Hall T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors Nature Communications |
| title | T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors |
| title_full | T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors |
| title_fullStr | T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors |
| title_full_unstemmed | T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors |
| title_short | T-cell stimulating vaccines empower CD3 bispecific antibody therapy in solid tumors |
| title_sort | t cell stimulating vaccines empower cd3 bispecific antibody therapy in solid tumors |
| url | https://doi.org/10.1038/s41467-023-44308-6 |
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