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A role for multiple chimeric antigen receptor-expressing leukocytes in antigen-specific responses to cancer
- Source :
- Oncotarget, Oncotarget, Impact journals, 2016, 7 (23), pp.34582-34598. ⟨10.18632/oncotarget.9149⟩
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 2016.
-
Abstract
- International audience; While adoptive immunotherapy using chimeric antigen receptor (CAR)-modified T cells can induce remission of some tumors, the role of other CAR-modified leukocytes is not well characterized. In this study, we characterize the function of leukocytes including natural killer (NK) cells, macrophages and CAR T cells from transgenic mice expressing a CAR under the control of the pan-hematopoietic promoter, vav, and determine the ability of these mice to respond to ERB expressing tumors. We demonstrate the anti-tumor functions of leukocytes, including antigen specific cytotoxicity and cytokine secretion. The adoptive transfer of CAR T cells provided a greater survival advantage in the E0771ERB tumor model than their wildtype (WT) counterparts. In addition, CAR NK cells and CAR T cells also mediated increased survival in the RMAERB tumor model. When challenged with Her2 expressing tumors, F38 mice were shown to mount an effective immune response, resulting in tumor rejection and long-term survival. This was shown to be predominantly dependent on both CD8(+) T cells and NK cells. However, macrophages and CD4(+) T cells were also shown to contribute to this response. Overall, this study highlights the use of the vav-CAR mouse model as a unique tool to determine the anti-tumor function of various immune subsets, either alone or when acting alongside CAR T cells in adoptive immunotherapy.
- Subjects :
- CD4-Positive T-Lymphocytes
Cytotoxicity, Immunologic
0301 basic medicine
Adoptive cell transfer
Receptor, ErbB-2
[SDV]Life Sciences [q-bio]
medicine.medical_treatment
T cell
Receptors, Antigen, T-Cell
T cells
Mice, Transgenic
NK cells
CD8-Positive T-Lymphocytes
Immunotherapy, Adoptive
Mice
03 medical and health sciences
Interleukin 21
0302 clinical medicine
Antigen
Cell Line, Tumor
Neoplasms
medicine
Animals
Cytotoxic T cell
Proto-Oncogene Proteins c-vav
chimeric antigen receptor
business.industry
Immunotherapy
Adoptive Transfer
Chimeric antigen receptor
macrophages
Killer Cells, Natural
Mice, Inbred C57BL
transgenic mouse
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Immunology
Interleukin 12
Cytokines
business
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....00e9e3dce26e76c8f880c4f7b5969a29