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[Fam-] trastuzumab deruxtecan (DS-8201a)-induced antitumor immunity is facilitated by the anti–CTLA-4 antibody in a mouse model
- Source :
- PLoS ONE, PLoS ONE, Vol 14, Iss 10, p e0222280 (2019)
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- [Fam-] trastuzumab deruxtecan (DS-8201a) is a HER2 (ERBB2)-targeting antibody-drug conjugate, composed of a HER2-targeting antibody and a topoisomerase I inhibitor, exatecan derivative, that has antitumor effects in preclinical xenograft models and clinical trials. Recently, [fam-] trastuzumab deruxtecan was reported to enhance antitumor immunity and was beneficial in combination with an anti-PD-1 antibody in a mouse model. In this study, the antitumor effect of [fam-] trastuzumab deruxtecan in combination with an anti-CTLA-4 antibody was evaluated. [Fam-] trastuzumab deruxtecan monotherapy had antitumor activity in an immunocompetent mouse model with EMT6 human HER2-expressing mouse breast cancer cells (EMT6-hHER2). [Fam-] trastuzumab deruxtecan in combination with the anti-CTLA-4 antibody induced more potent antitumor activity than that by monotherapy with either agent. The combination therapy increased tumor-infiltrating CD4+ and CD8+ T cells in vivo. Mechanistically, cured mice with treatment of [fam-] trastuzumab deruxtecan and an anti-CTLA-4 antibody completely rejected EMT6-mock cells similar to EMT6-hHER2 cells, and splenocytes from the cured mice responded to both EMT6-hHER2 and EMT6-mock cells as measured by interferon-gamma release. Taken together, these results indicate that antitumor immunity is induced by [fam-] trastuzumab deruxtecan and is facilitated in combination with anti-CTLA-4 antibody.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
Immunoconjugates
Receptor, ErbB-2
Physiology
Cancer Treatment
CD8-Positive T-Lymphocytes
Biochemistry
Mice
White Blood Cells
chemistry.chemical_compound
Spectrum Analysis Techniques
0302 clinical medicine
Animal Cells
Trastuzumab
Immune Physiology
Medicine and Health Sciences
CTLA-4 Antigen
Enzyme-Linked Immunoassays
skin and connective tissue diseases
Immune System Proteins
Multidisciplinary
biology
T Cells
Chemistry
Animal Models
Flow Cytometry
Experimental Organism Systems
Oncology
Spectrophotometry
030220 oncology & carcinogenesis
Monoclonal
Medicine
Female
Cytophotometry
Cellular Types
Antibody
Research Article
medicine.drug
Combination therapy
Science
Immune Cells
Immunology
Breast Neoplasms
Mouse Models
Cytotoxic T cells
Antibodies, Monoclonal, Humanized
Research and Analysis Methods
Antibodies
03 medical and health sciences
Model Organisms
In vivo
Cell Line, Tumor
Splenocyte
medicine
Animals
Humans
Exatecan
Immunoassays
Immunohistochemistry Techniques
neoplasms
Cell Proliferation
Blood Cells
Biology and Life Sciences
Proteins
Cell Biology
Immunity, Innate
Histochemistry and Cytochemistry Techniques
Disease Models, Animal
030104 developmental biology
Animal Studies
Immunologic Techniques
Cancer research
biology.protein
Camptothecin
CD8
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....5d6f907ac2dbb1b3031422540ac56572