Juergen Hess
Head of
Scientific Affairs, responsif GmbH, Schallershofer Str. 84, D-91056 Erlangen,
Germany. hess@responsif.de,
http://www.responsif.de
responsif’s main objectives
are to discover new biologically-based therapies in oncology and to pursue
the clinical development of already identified candidates. Our novel immunotherapeutic
concept against cancer is focussed on the application of autologous and apoptotic
tumor cells coated with chicken annexin-V (AxV) as immune response-modifying
protein. Tumour vaccines prepared of autologous
apoptotic cancer cells are usually rapidly eliminated by macrophages after
administration via anti-inflammatory phagocytosis and therefore they do not
result in an efficient sensitization of the immune system to the tumour. In
contrast, by the addition of AxV this non-immunogenic removal of the apoptotic
tumour cells is efficiently counteracted leading to prominent anti-tumour
effects. A clinical proof-of-concept
study to demonstrate the efficacy of this treatment is already under way for
patients suffering from renal cell carcinoma. It is worth mentioning that
responsif’s treatment concept can be applied to various types of cancer.
The
second R&D focus of responsif is represented by our murine
polyomavirus-like-particle technology (PLP), which can be applied to peptide
and protein delivery for preventive and therapeutic immunisations in various
fields of use. In close cooperation with our partners we are working on
novel therapeutic concepts against breast cancer and melanoma by using heterologous
PLP-mediated vaccinations for inducing antigen-specific CD8 T cell responses
in animal models. Our PLP technology is generally based on the Escherichia coli expression system, subsequent protein purification
steps and the final in vitro co-assembling process of subunits
into capsoids. Heterologous PLP derivatives could be used for the display
of more hydrophobic T cell epitopes at the c-terminal end of VP1 coat protein.
For protein delivery, we favour our PLP anchoring
technology, which allows the in vitro packaging of complete
proteins (e.g. for proof-of-principle: green fluorescent protein) as VP2-entities
into the PLP-shells.