Autologous therapeutic vaccine APAVAC®

You are familiar with, and may already have used, the APAVAC kit, the effectiveness of which has been demonstrated for more than 10 years and more than 1000 animals treated in various indications, and the results and safety of which have been published by several university teams. (1–5)

This kit has been specially designed to enable veterinary surgeons to prepare an anti-cancer treatment based on a tumour biopsy, simply and on an autonomous basis.

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

1. Tumour 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 tumour antigens?

Tumour cell instability

Because tumour cells are genetically unstable, they synthesise modified proteins that are antigens normally recognised by the immune system. Tumour Specific Antigens (TSAs).

Unlike shared antigens, which exist in many individuals, personalised antigens are unique to a patient and are most often neo-epitope ASTs. (6). Targeting personalised antigens enables exclusive specificity and releases T cells that bypass negative selection and produce generalised T cell reactivity in patients who respond to treatment.

It is this principle of a vaccine with a predefined personalised antigen that is used in the APAVAC treatment..

Tumour heterogeneity

Furthermore, the immune behaviour of tumour masses is highly heterogeneous, varying not only according to tumour type, stage and treatment regimen, but also on an inter-individual basis. (7). Finally, the tumour microenvironment, because of its heterogeneity, has relatively effective immunosuppressive capacities.

Various phenomena relating to tumour progression, such as tumour angiogenesis and epithelial-mesenchymal transition, have been described for their links with the tumour's immunosuppressive capacity.

Importance of the first extraction stage in preparing the treatment

The prerequisite for preparing the APAVAC® treatment (extraction stage) is therefore :

1. to "dissect" the tumour sample in order to crush it and separate the tumour cells from the abundant non-malignant cellular compartment (stroma, connective tissue, endothelium, etc.), using the scalpel, pliers and crushing tubes supplied sterile and ready to use in the kit

2. destroy tumour cell membranes to extract Tumour Specific Antigens (TSAs), using hypertonic Na2CO3 solution A

3. cryoprecipitate the small proteins represented by the ATSs from the cell debris using saturated (NH4)2 SO4 solution B.

It is these tumour antigens, combined with the heat shock proteins (HSPs) and then fixed, concentrated and vectorised by the hydroxyapatite beads, that 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.

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: + 33 5 34 47 86 10

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Autologous therapeutic vaccine APAVAC®​