Rationale of basing immunotherapies on Long Synthetic Peptides (LSPs)
Long peptides are very attractive for the development of cancer immunotherapies as they enable the generation of both strong and long-lasting CD4+ and CD8+ T-cell responses in humans while overcoming induction of immune tolerance. In addition, thanks to their fully synthetic composition, LSPs have the strong advantage of being safe and easy to manufacture compared to “biological vaccines” created from living organisms.
In 16 clinical trials in which Vaxeal executives participated, LSP-based vaccines were found to be safe, well tolerated and showed promising clinical efficacy in patients with pre-neoplastic lesions.
Use of promiscuous T-Cell epitopes
Promiscuous CD4+ T-cell epitopes correspond to sequences able to induce an immune response in multiple donors.
Vaxeal chose to develop immunotherapies that activate both CTLs and CD4+ T-cells as they have been found to be more effective than vaccines that only target CD8+ T-cell responses because of the action of CD4+ T-cells on both CTL and humoral responses. In addition, CD4+ T-cell responses play also an essential role in cellular immunity against cancer cells by contributing to production of an inflammatory micro-environment that favors immune cell recruitment around the tumors.
Use of fixed combined immunotherapies
Cancer cells suppress the immune system which enables it to form a sustainable tumor mass. Tumors develop immunosuppressive mechanisms in the tumor microenvironment, such as:
- Endothelial cell barriers limiting T-cell extravasation and instability of the functional competence of T-cells at the tumour site,
- Induction of regulatory cells (Regulatory CD4+ T-cells (Treg), Myeloid-derived suppressor cells or MDSCs), and
- Co-opting of immune checkpoint pathways to suppress the anti-tumoral immune response in the tumour microenvironment.
Recently, some standard cancer therapies and some immunomodulators, such as immune checkpoint blockade therapies, have been found to modulate tumour-induced immune suppression.
Therefore, to increase further the efficacy of its vaccine candidates, Vaxeal intends to combine them with such standard cancer therapies as well as a combination with immune checkpoint proteins blockers.