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UCPVax : a UCP Vaccine enhancing CD4+ response

Using specific cancer markers to turn “cold” tumors “hot”

Cells will express on their surface short protein fragments – peptides – corresponding to proteins that are active within them. Cancer cells are no exception and express peptides, recognizable by the immune system, of the telomerase enzyme. These peptides serve as antigens for Invectys’ UCPVax.
UCPVax stands for Universal Cancer Peptide Vaccine, a therapeutic vaccine currently in Phase I/II in Metastatic Non-Small Cell Lung Cancer, with potential applications in a broad range of cancer indications.

Telomerase peptides are expressed virtually only on the surface of cancer cells, making them a clear-cut target. UCPVax is a vaccine based on these peptides, with the objective of triggering an immune response against them. In fine, the immune system will recognize tumor cells as targets and create an adaptive response against them.

More specifically, this vaccine uses 4 different peptides (UCP1 through 4) to trigger the activation of CD4+ T-Helper cells (in this case, T-Helper 1 cells, or TH1) specific to these peptides. These cells act as coordinators and regulators of the adaptive immune response. Through the production of chemical messengers such as IFN-γ and TNFα, the T-Helpers stimulate the growth and Cytotoxic T Lymphocytes (CTLs).
UCPVax has been shown to induce strong TH1 CD4 T Cell response, which was associated with increased CTL response.

Pre-clinical results

UCPVax has demonstrated encouraging results in in vitro and in vivo preclinical studies:

  • Proliferation of Th1 cells and production of Th1 cytokines (IL-2, IFN-γ, TNFα)
  • Specificity of the immune response confirmed
  • Increased tumor-specific CD8+ T-Cell response against the UCP used
  • Activation of dendritic cells
  • Safety: no significant vaccine-related toxicity

UCPVax has also demonstrated, in early clinical results, an increased CD4+ response against hTERT peptides in 60% of cases.

UCPVax Mechanism of Action

1) UCPVax (A), containing UPC helper peptides and CTL peptides, is injected intradermaly.

2) Dendritic cells, or DCs (B) absorb the peptides and present them at their surface. UCP helper peptides are presented by the MHC*-II, while CTL peptides are presented by the MHC-I.

3) The DC simultaneously presents the peptides to two immune cells specific to these peptides, and activates them:
– UCP helper peptides are presented to unspecialized T-helper cells (C)
– The CTL peptides are presented to CTL cells (D)

4) In this 3-cell structure, the DC produces Interleukin 12, or IL-12, which induces the differentiation of the unspecialized T-helper cell into a Th1 cell.

5) Stimulated by IL-12, the Th1 cell will produce IFN-γ (a tumor-inhibiting molecule) and GM-CSF to further activate the DC.

6) Meanwhile, CTLs are activated by the presentation of CTL peptides. The Th1 will also produce IL-2 which, with IFN-γ, stimulate the growth of CTLs.

7) Activated CTLs move to the tumor location.

8) On contact with tumor, and stimulated by local anti-UCP Th1s (E) (again producing IFN-γ and IL-2), the CTLs will target and destroy cancer cells.

*MHC: Major Histocompatibility Complex

UCPVax Mechanism of Action