Introduction/Background*Ovarian cancer (OC) causes high mortality due to late diagnosis and high rate of relapse following initial therapy. Immunotherapy in combination with standard treatment modalities forms a promising new treatment approach.
DCP-001 is an intradermally applied cancer relapse vaccine derived from the human leukaemic cell line DCOne® and is currently tested in acute myeloid leukaemia patients. To obtain the highly immunogenic DCP-001 vaccine, DCOne cells are shifted towards a mature dendritic cell phenotype. Since DCOne cells express multiple common tumour associated antigens such as WT-1, RHAMM, PRAME and MUC-1, which are also documented as target antigens in OC, DCP-001 vaccination may also be efficacious in OC. To support this hypothesis, the capacity of DCP-001 to induce immune responses against OC was studied in human peripheral blood mononuclear cells (PBMCs) from OC patients and a humanized mouse model for OC.
Methodology The effect of DCP-001 on T cells was evaluated after a 3 week culture of PBMCs with or without DCP-001. Cytotoxic activity was analysed by IFNγ production and CD107a expression when these cells were subsequently cultured with OC cell line SKOV3. The effect of DCP-001 vaccination in vivo was evaluated in humanised NCG mouse subcutaneously engrafted with SKOV3 OC cells. Mice received two intra-peritoneal (i.p.) vaccinations with DCP-001 either after or prior to SKOV3 engraftment and tumour size was measured to evaluate the efficacy of DCP-001.
Result(s)* In vitro, DCP-001 was shown to activate both CD4+ as well as CD8+ T cells and to induce formation of memory T cells. Importantly, DCP-001-stimulated CD8+ T cells from OC patients were shown to exert a HLA class I dependent, immune response to OC cells. In vivo, in an ovarian tumour mouse model, significant reduction of tumour growth rate and partial or even complete tumour regressions were observed in mice vaccinated with DCP-001, particularly when administered as relapse vaccine (prior to tumour engraftment), as compared to PBS treated mice.
Conclusion*These pre-clinical in vitro and in vivo results support the potential use of DCP-001 as a cancer relapse vaccine in ovarian cancer, with the aim to reduce disease recurrence following initial standard of care therapy.
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