Stock DZ
04.06.2018 kl 22:32

fimaVacc as described by Arctic,hopefully this is investor friendly language

FimaVACC is in development for the enhancement of immunological responses to therapeutic cancer (peptide) vaccines. The fimaVACC technology aims to induce an effective boost of CD8+ killer Tcells or cytotoxic T-lymphocytes (CTLs), which are known to be key to realize the potential of therapeutic cancer vaccination. Cancer vaccines are intended to play an important role in immunotherapy of a wide range of solid tumor indications in the future, as it is the only way to induce a specific immune response to chosen targets. However, the development of clinically efficacious therapeutic peptide vaccines has been shown to be challenging in practice and especially the delivery and the potentiation of an adequate immune response has been shown to be difficult.

**************fimaVACC mode of action***************
Vaccines aimed at stimulating CD8+ T-cell responses are typically ineffective because the MHC classII and not the MHC-I class primarily process vaccine antigens for antigen presentation. The latter requires cytosolic delivery of antigen. To induce a potent immune response, immune cells need to be attracted to the site of vaccination and boosted sufficiently. At least two parameters are known to be important, i) the immunogenicity of the technology platform and ii) the delivery or route of administration of the cancer vaccine. Even if peptide vaccines have been optimized to this end, they are still not very immunogenic inherently and an adjuvant is needed to attract antigen presenting cells (APCs) to the site of vaccination. When taken up in APCs by a more random event, the vaccine antigens are processed and then presented on the surface of the APCs in different molecules that will induce the generation of different antigen (or disease) specific immune T-cells:
1- CD8+ killer T-cells or cytotoxic T-lymphocytes (CTLs) that directly attack cancer (or virusinfected) cells
2- CD4+ T-cells are needed for optimal and sustained effector CD8 T-cell responses as well as the induction and maintenance of CD8+ memory cells
Peptide vaccines are shown to induce mostly a CD4+ T cell response due to antigen processing via the endosomal pathway in APCs. Through disruption of the endosomal pathway with fimaVACC, PCIB is looking to release antigens in the cytosol and thereby stimulate processing of antigens via the alternative, proteasomal degradation pathway. By making antigens accessible for the MHC class I presentation machinery, one could induce a CD8+ killer T-cell specific response (see figure below). Therefore, the fimaVACC technology may provide a solution to the underlying challenge with peptide vaccines as a technology platform, and substantially improve the ability of vaccines to trigger the immune system to fight cancers and infectious diseases

**************Preclinical data of fimaVACC shows to enhance the immune response**********
PCI Biotech has generated impressive preclinical data on enhancement of different therapeutic model vaccines in mice, indeed showing a clear shift in the number of CD8+ killer T cells induced when combining vaccination with a therapeutic HPV vaccine and fimaVACC. FimaVACC was shown to induce >20 and >40 times enhancement of antigen-specific CD8+ T-cells in spleen and blood cells,
respectively, as shown in the figure below.

****************fimaVACC strongly enhances effects of vaccination**************
In other preclinical models fimaVACC showed to substantially enhance not only CD8+ T cell enhancement (9 times), but also CD4+ T-cell (5 times) and antibody responses (9 times) tovaccine/adjuvant combinations. A study with a key reference protein for vaccination experiments, ovalbumin, combined with fimaVACC in an aggressive B16-OVA melanoma tumor model, showed significantly more reduction in tumor volume than compared to vaccination with the tumor cell antigen alone (see figure)

***************Therapeutic vaccination in tumor mouse model*****************
Preclinical data of fimaVACC were published in peer-reviewed journals (Waeckerle-Men et al, Eur J Pharm Biopharm, 2013 Håkerud et al, J Control Release, 2014 Håkerud et al, J Control Release, 2015). Based on promising preclinical results, PCI Biotech filed several new patent applications for fimaVACC.
The company was awarded a NOK 12.5m BIA grant from the Norwegian Research Council for the period 2014-2017 and another NOK 13.8m for the period 2017-2020 to develop the fimaVACC technology and document clinical proof-of-principle. In addition, PCI Biotech has an ongoing preclinical research collaboration with Ultimovacs, a Norwegian biotech company developing a therapeutic cancer vaccine targeting telomerase, for which it received NOK 500,000 from Innovation Norway and Oslo Cancer Cluster.
Redigert 04.06.2018 kl 22:33 Arkivert