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The novel bispecific diabody alphaCD40/alphaCD28 strengthens leukaemic dendritic cell-induced T-cell reactivity.
- Source :
-
British journal of haematology [Br J Haematol] 2008 Jun; Vol. 142 (2), pp. 273-83. Date of Electronic Publication: 2008 May 19. - Publication Year :
- 2008
-
Abstract
- Dendritic cell (DC)-based immunotherapy faces new challenges because the efficacy of DC vaccines in clinical trials has been inconsistent. Strategies to improve immune responses induced by DC are currently being explored. We have recently shown the feasibility of generating fully functional DC from acute myeloid leukaemic (AML) blasts, but with varying expression levels of the important costimulatory molecule CD86. To overcome this variability, we developed a novel bispecific diabody that simultaneously and agonistically targeted CD40 on AML-DC and CD28 on naïve T cells. Beside optimization of CD28-mediated signalling, the resulting cellular cross-linking was also hypothesized to increase the strength and duration of T cell/AML-DC interactions, thus increasing T-cell responsiveness to AML antigens. The alphaCD40/alphaCD28-bispecific diabody was found to bind to its target antigens and provoked increased T-cell-DC cluster formation. The alphaCD40/alphaCD28 diabody is capable of increasing T-cell proliferation induced by AML-DC as well as the induction of DC maturation. Importantly, priming efficacy of tumour-specific cytotoxic T cells can also be improved by cross-linking AML-DC and T cells with the alphaCD40/alphaCD28 diabody. We propose that the alphaCD40/alphaCD28-bispecific diabody can serve as a potent therapeutic tool to effectively augment anti-tumour T-cell responses elicited by AML-DC.
- Subjects :
- Antibodies, Bispecific biosynthesis
Antibodies, Bispecific immunology
CD8-Positive T-Lymphocytes metabolism
Cell Proliferation
Dendritic Cells cytology
Dendritic Cells immunology
Flow Cytometry
Humans
Leukemia, Myeloid, Acute pathology
Leukemia, Myeloid, Acute therapy
T-Lymphocytes, Cytotoxic immunology
Antibodies, Bispecific therapeutic use
Antigens, Neoplasm immunology
CD28 Antigens immunology
CD40 Antigens immunology
Cancer Vaccines immunology
Immunotherapy methods
Leukemia, Myeloid, Acute immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2141
- Volume :
- 142
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- British journal of haematology
- Publication Type :
- Academic Journal
- Accession number :
- 18492117
- Full Text :
- https://doi.org/10.1111/j.1365-2141.2008.06990.x