Abstract
We have developed an individualized melanoma vaccine based on autologous dendritic cells (DCs) transfected with autologous tumor-mRNA. The vaccine targets the unique spectrum of tumor antigens in each patient and may recruit multiple T cell clones. In a recent phase I/II trial, we demonstrated T cell responses against vaccine antigens in 9/19 patients evaluable by T cell assays. Here, we report a follow-up study that was conducted to characterize interesting T cell responses and to investigate the effects of long-term booster vaccination. Two patients were selected for continued vaccine therapy. The clinical follow-up suggested a favorable clinical development in both patients. The immunological data (T cell proliferation/IFNγ ELISPOT/Bioplex cytokine assays) indicated sustained T cell responses and suggested an enhancing effect of booster vaccinations. Both CD4+ and CD8+ T cell responses were demonstrated. From post-vaccination samples, we generated 39 T cell clones that responded specifically to stimulation by mRNA-transfected DCs and 12 clones that responded to mock-transfected DCs. These data clearly indicate a two-component vaccine response, against transfected and non-transfected antigens. T cell receptor (TCR) clonotype mapping, performed on 11 tDC-specific clones, demonstrated that 10/11 clones had different TCRs. The results thus indicate a broad spectrum T cell response against antigens encoded by the transfected tumor-mRNA. We generally observed mixed Th1/Th2 cytokine profiles, even in T cell clones that were confirmed to be derived from a single cell. This finding suggests that cytokine patterns after cancer vaccination may be more complex than indicated by the classic Th1/Th2 dichotomy.
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Abbreviations
- DC:
-
Dendritic cell
- PBMC:
-
Peripheral blood mononuclear cell
- TCR:
-
T cell receptor
- DTH:
-
Delayed-type hypersensitivity
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This work was supported by the Norwegian Ministry of Health (Gene Therapy Grant), the Norwegian Cancer Society and ENACT.
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Kyte, J.A., Kvalheim, G., Lislerud, K. et al. T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells. Cancer Immunol Immunother 56, 659–675 (2007). https://doi.org/10.1007/s00262-006-0222-y
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DOI: https://doi.org/10.1007/s00262-006-0222-y