INVAC-1 : A DNA vaccine targeting cancer

• 20 advanced cancer patients injected monthly with electroporation
  • 3 cohorts with 100, 400 and 800 µg doses of INVAC-1
    (n=3 per cohort)
  • Extension cohort 800 µg (n=11)
  • 3 cycles per protocol
• 6 additional patients injected with needle-free injection device

• Toxicity, tolerance, safety and immune responses
• Efficiency and immune response duration

• Vaccine treatment was safe and well tolerated
• No Dose Limiting Toxicity observed

• 1-year survival reached for 65% of patients
• 60% of patients demonstrated stabilized disease
• Overall median survival of 15 months
• Overall PFS was 2,7 months
• 6 patients remain alive as of November 2019

• Uncompromised immune system
• Duration: 6 doses of INVAC-1 as single agent injected at 4 week intervals for 6 months with follow-up of 2 years

• Expected synergy with Ibrutinib
• Duration: 6 doses of INVAC-1 as single agent injected at 4 week intervals for 6 months with follow-up of 2 years

1) Preparing a vehicle for the hTERT DNA

INVAC-1 contains the DNA to produce human telomerase. Since telomerase gives its properties to tumor cells, Invectys’ version is slightly modified to avoid any risks: its functional component is inactivated, and it is designed to be rapidly broken down by the cell machinery. This DNA is injected intradermally through small, circular DNA strands called plasmids (A).

2) Making immune cells produce telomerase

The plasmids are forced into an Antigen Presenting Cell (APC) (B). INVAC-1 then finds its way to the nucleus of the APC, where it remains in episomal form (it is not integrated in the chromosomes, but is still expressed by the cell). Thus, the APC will start producing Invectys’ modified telomerase.

3) Breaking down and expressing telomerase

Because this modified telomerase is designed to be degraded, the APC will break it down into small components (peptides). These peptides will then migrate to the surface of the cell, where they will be presented by protein structures known as MHC-I (C) and MHC-II (D). It is important to note that MHC-I (aka HLA-1) can be found on all human cells, while MHC-II (aka HLA-2) is only expressed by certain immune cells.

4) Activating specialized T-Cells

With these telomerase peptides at its surface, the APC will migrate to the lymph nodes, where it will meet several categories of T-Cells: CD4+ T-helper cells (Th) (E), which stimulate the growth and the potency of other immune cells, and CD8+ Cytotoxic T Lymphocytes (CTL) (F), which eliminate dangerous cells. In the case of INVAC-1, these will be tumor cells. The antigen carried by the MHC-I will activate the CTLs, while the same antigen carried by the MHC-II will activate the T-helpers.
Because the immune response is highly specific, each peptide will activate a different set of Th and CTL cells.

5) Enabling Cytotoxic T-Cells

Once activated, the T-helper cells will produce cytokines, chemical messengers that will trigger the activation, growth and killing activity of the CTLs.

6) Recognizing telomerase on tumor cells

Like regular cells, tumor cells express a variety of peptides on their surface, thanks to the MHC complexes. The telomerase (G) in a tumor cell will be degraded by the proteasome (H), and presented by the cell’s MHC-I (I).

Since the body now produces active CTLs, able to recognize telomerase peptides, the CTLs will be able to bind with the peptide-carrying MHCs.

7) Destroying the cancer cells

Once attached to the cancer cell, the CTL will secrete a number of proteins (J), which will trigger a series of phenomena, leading to the death of the tumor cell.