Autologous therapeutic vaccine APAVAC®

You may already be familiar with and have used the APAVAC kit, whose effectiveness has been demonstrated for over 10 years, with more than 1,000 animals treated in various indications, and whose results and safety of use have been published by several university teams. (1–5)

This kit has been designed to enable a veterinarian to prepare an anti-cancer treatment from a tumor biopsy, easily and independently.

The principle of this treatment is to activate a specific immunotherapy against the tumor and/or its possible metastases by relying on three elements essential to its functioning:

1. Tumor Specific Antigens (TSAs),

2. Heat Shock Proteins (HSPs)

3. Hydroxyapatite.

We wanted to give you a clear and precise explanation of the role of each of these components.

Why tumor antigens ?

Reminder

Tumor-specific antigens are proteins that need to be extracted from tumor cells, and in particular from their membranes. The first steps in preparing APAVAC treatment are to select and isolate these proteins to trigger the activation of cytotoxic T lymphocytes against tumor cells. (1-7).

To be continued in our latest Newsletter...

Why Heat Shock Proteins ?

Molecular chaperone function

Heat Shock Proteins are molecular chaperones. Molecular chaperones bind and stabilize proteins at intermediate stages of folding, assembly, translocation across membranes and degradation. HSPs are among the most highly conserved proteins in the living kingdom, and are classified according to their molecular weight.

Cancer cells under metabolic stress synthesize large quantities of stress proteins, which are also found in the blood (8), according to Ciocca et al.

In addition to their role in stabilizing proteins under conditions of cellular stress, HSPs are also involved in triggering the immune response.

Peptide antigen binding

Hsp70 and gp96 transport peptide antigens, which are chaperoned by these proteins for presentation to immune system cells: peptides generated in the cytoplasm are transported across the endoplasmic reticulum membrane by antigen-priming associated transporters (TAPs), loaded into MHC class I proteins and presented to cytotoxic CD8+ T lymphocytes. (9).

In addition, the uptake of HSPs by Antigen Presenting Cells (APCs) leads to the maturation of these cells and the synthesis of cytokines that activate the immune response.

The aim of the APAVAC treatment is to purify these proteins from tumor tissue onto hydroxyapatite particles, which are then injected subcutaneously into the patient. These particles act as purification elements, adjuvants and vectors for the proteins in the Antigen-Presenting Cells (APCs).

Demonstrating the role of HSP110

To demonstrate and prove the predominant role of HSPs in the mode of action of APAVAC treatment, we developed tumours in a mouse model previously rendered incapable of synthesising a large HSP (HSP110), known for its high affinity for tumour antigens.

The complete APAVAC vaccine (obtained from wild-type WT mice) compared with the vaccine obtained from HSP110-depleted mice (APAVAC shHSP110) was significantly more effective in terms of tumour volume reduction, as confirmed by analysis of tumour cell apoptosis.

These tumour antigens, combined with heat shock proteins (HSPs) and then fixed, concentrated and vectorised by the hydroxyapatite grains, will activate the animal's specific immune system against its own tumour.

To be continued in our next Newsletter...

REFERENCES

1. Marconato L, Frayssinet P, Rouquet N, Comazzi S, Leone VF, Laganga P, et al. Randomized, placebo-controlled, double-blinded chemoimmunotherapy clinical trial in a pet dog model of diffuse large B-cell lymphoma. Clin Cancer Res Off J Am Assoc Cancer Res. 1 févr 2014;20(3):668‑77.
2. Marconato L, Stefanello D, Sabattini S, Comazzi S, Riondato F, Laganga P, et al. Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma. Vaccine. 22 sept 2015;33(39):5080‑6.
3. Marconato L, Aresu L, Stefanello D, Comazzi S, Martini V, Ferrari R, et al. Opportunities and challenges of active immunotherapy in dogs with B-cell lymphoma: a 5-year experience in two veterinary oncology centers. J Immunother Cancer. 7 juin 2019;7(1):146.
4. Frayssinet P, Mathon D, Simonet M, Trouillet J, Mathon V, Rouquet N. TREATMENT OF CANINE OSTEOSARCOMA USING AUTOLOGOUS ACTIVE IMMUNOTHERAPY WITH OR WITHOUT SURGERY. In 2020. p. 183‑97.
5. Sayag D, Jacques D, Thierry F, Castell Y, Aumann M, Gauthier O, et al. Combination of CT-Guided Microwave Ablation and Cementoplasty as a Minimally Invasive Limb-Sparing Approach in a Dog with Appendicular Osteosarcoma. Animals [Internet]. 2023;13(24). Disponible sur: https://www.mdpi.com/2076-2615/13/24/3804
6. Lin MJ, Svensson-Arvelund J, Lubitz GS, Marabelle A, Melero I, Brown BD, et al. Cancer vaccines: the next immunotherapy frontier. Nat Cancer. août 2022;3(8):911‑26.
7. Sautès-Fridman C, Cherfils-Vicini J, Damotte D, Fisson S, Fridman WH, Cremer I, et al. Tumor microenvironment is multifaceted. Cancer Metastasis Rev. mars 2011;30(1):13‑25.
8. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. Summer 2005;10(2):86‑103.
9. Schuette V, Burgdorf S. The ins-and-outs of endosomal antigens for cross-presentation. Curr Opin Immunol. févr 2014;26:63‑8.
10. Ciocca DR, Frayssinet P, Cuello-Carrión FD. A pilot study with a therapeutic vaccine based on hydroxyapatite ceramic particles and self-antigens in cancer patients. Cell Stress Chaperones. Spring 2007;12(1):33‑43.

Find out more?

Would you like to discuss the use of APAVAC® on an animal in your care?

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Contact us by e-mail: sciences@hastim.fr or by telephone: 05 34 47 86 10

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Autologous therapeutic vaccine APAVAC®​