Kurzfassung

Talimogene laherparepvec was engineered from herpes simplex 1 (HSV-1). Herpes Simplex Virus Type (HSV) belongs to Herpesviridae family12. It is a double stranded DNA virus that contains three main structural components (central core, inner core, capsid). Genetic modifications were made to the virus in order to attenuate the virus and increase selectivity for cancer cells.
Our different ex vivo human melanoma models enable the direct characterization of T-VEC-induced TCLs for their means to...Talimogene laherparepvec was engineered from herpes simplex 1 (HSV-1). Herpes Simplex Virus Type (HSV) belongs to Herpesviridae family12. It is a double stranded DNA virus that contains three main structural components (central core, inner core, capsid). Genetic modifications were made to the virus in order to attenuate the virus and increase selectivity for cancer cells.
Our different ex vivo human melanoma models enable the direct characterization of T-VEC-induced TCLs for their means to activate and improve maturation of iDCs and to stimulate human immune cells, such as CTL and CD4 cells or to block T-reg cells.
We isolate primary human immune cells from buffy coats of healthy blood donors to coculture them with different melanoma cells incubated with T-VEC and later with HLA-A2 corresponding T-cells for their means to differentiate DC and activate CTL. The coincubation of DCs can also be done with control vectors,non-replicative viruses or in combination with chemotherapeutic drugs as well as with other immunogenic target agents.
Read out and quantification of antigen directed CTL responses will be based on the distinct methods as described (see Materials and Methods). The inhibiton of negative T-regs can also be analysed.
Furthermore, we characterize the DC-mediated TAA cross-presentation in more details after phagocytosis of T-VEC infected melanoma TCLs. Here, interaction of damage-associated molecular patterns (DAMPs) with various receptors like Toll-like receptors (TLRs) are required to evoke immunogenic cell death (ICD)-induced anti-tumor immune responses30. Therefore, we analyse the functional role of TLRs and their signaling pathways resulting in DC-activation after incubation with T-VEC infected melanoma cells.
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