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Novel Bispecific Antibodies Increase γδ T-Cell Cytotoxicity against Pancreatic Cancer Cells.
- Source :
-
Cancer Research . Mar2014, Vol. 74 Issue 5, p1349-1360. 12p. - Publication Year :
- 2014
-
Abstract
- The ability of human γδ T cells from healthy donors to kill pancreatic ductal adenocarcinoma (PDAC) in vitro and in vivo in immunocompromised mice requires the addition of γδ T-cell-stimulating antigens. In this study, we demonstrate that γδ T cells isolated from patients with PDAC tumor infiltrates lyse pancreatic tumor cells after selective stimulation with phosphorylated antigens. We determined the absolute numbers of γδ T-cell subsets in patient whole blood and applied a real-time cell analyzer to measure their cytotoxic effector function over prolonged time periods. Because phosphorylated antigens did not optimally enhance γδ T-cell cytotoxicity, we designed bispecific antibodies that bind CD3 or Vγ9 on γδ T cells and Her2/neu (ERBB2) expressed by pancreatic tumor cells. Both antibodies enhanced γδ T-cell cytotoxicity with the Her2/Vγ9 antibody also selectively enhancing release of granzyme B and perforin. Supporting these observations, adoptive transfer of γδ T cells with the Her2/Vγ9 antibody reduced growth of pancreatic tumors grafted into SCID-Beige immunocom-promised mice. Taken together, our results show how bispecific antibodies that selectively recruit γδ T cells to tumor antigens expressed by cancer cells illustrate the tractable use of endogenous γδ T cells for immunotherapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BISPECIFIC antibodies
*IMMUNOGLOBULINS
*T cells
*LYMPHOCYTES
*PANCREATIC cancer
Subjects
Details
- Language :
- English
- ISSN :
- 00085472
- Volume :
- 74
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 94903395
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-13-0675