Dendritic Cell-Based Vaccine (DC-Based Vaccine)
Dendritic cells (DCs) fulfill an important function in immune defense through capturing, processing and presenting antigens on their cell surface, thus eliciting in T cells a specific immune response against the antigen presented. This capability can be utilized to elicit immune responses against certain molecules on tumor cells, particularly tumor stem cell antigens including ABCB5, and thus overcome immune tolerance against the tumor. For this purpose, DCs are loaded with the respective tumor antigen, resulting in a DC-based vaccine tailored to each individual patient. Various DC vaccines have already been investigated as potential curative therapies for cancer with some promising results being shown.
Production of a DC vaccine for the treatment of ABCB5-expressing tumors.
An optimized protocol for generation of dendritic cells using a leukapheresis as starting material has been established and scaled up for production of a DC-based vaccine according to current good manufacturing practice (GMP) for use in clinical trials.
Using bioinformatic analyses, immunogenic epitopes (i.e. the regions of an antigen that are recognized and bound by T cells, usually peptides of 9 to 15 amino acids) in the ABCB5 molecule have been identified. Immunogenicity of the selected epitopes was demonstrated by the induction of a T cell response against ABCB5 in vitro using cells from healthy donors. Furthermore, ABCB5-reactive T cells could be detected in melanoma patients, underlining the eligibility of ABCB5 as target antigen in cancer immunotherapy (Borchers et al., 2017).
The peptides to load DCs and thus generate an ABCB5-specific vaccine are currently produced according to GMP by a specialized contractor.