Autologous therapeutic vaccine APAVAC®
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Reminder
Tumour-specific antigens are proteins that need to be extracted from tumour cells and particularly from their membranes. The first steps in preparing APAVAC treatment involve selecting and isolating these proteins to trigger the activation of cytotoxic T lymphocytes against tumour cells. (1-7).
Read more in our latest Newsletter... |
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Why Heat Shock Proteins ? |
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Reminder
Heat Shock Proteins (HSPs) are molecules that react to cellular stress and oppose abnormal protein folding. They are known to modulate immune responses. In a stressful environment, such as a tumour, HSPs are up-regulated and highly expressed in tumour cells. (8,9). They have an affinity and, because of their function, can bind to tumour antigens. It is this HSPs/ATSs complex that binds to the hydroxyapatite granules and is re-injected into the animal to access the antigen presenting cells (APCs)..
Read more in our latest Newsletter...
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Why hydroxyapatite particules ? |
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Immunostimulating adjuvant
Hydroxyapatite particles have the ability to bind specifically to the protein complexes associated with HSPs and the property of acting as an adjuvant in the immunostimulation (or vaccination) process. They have a specific physical property and, like most ceramics, are made up of grains of material bound together by grain boundaries. When these particles or fragments are phagocytosed by cells in their low pH compartments, the grain boundaries are broken down and the micro/nanoparticles are released into the cell until they are completely dissolved.. |
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Vectorization of the HSPs/ASTs complex
Purification of HSPs by adsorption chromatography on hydroxyapatite particles enables them to be concentrated on a perfectly biocompatible support without the need to desorb the proteins from the particles. Instead, the particles can be used to vectorise the proteins into the CPAs. It is possible to deliver the proteins carried by the particles directly into the APCs. We have shown that injection of HAP particles into rat subcutaneous tissue resulted in an influx of monocytes, macrophages and dendritic cells (10). Furthermore, when particles were injected into connective tissue, we demonstrated that they were capable of transfecting (transferring a gene) towards the monocytic cells that make up the foreign body response and potentially present the antigen (11). These same cells migrate away from the foreign body response and retain their functionality. |
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The physico-chemical and mechanical characteristics of APAVAC® hydroxyapatite grains have been specifically developed to select, concentrate and bind tumour antigens, combined with heat shock proteins, onto a support that will be injected into the animal according to a precise vaccination schedule. |
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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.
11. Frayssinet P, Rouquet N, Mathon D. Bone
cell transfection in tissue culture using hydroxyapatite microparticles. J
Biomed Mater Res A. nov 2006;79(2):225‑8.
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Les 4 points forts de l’immunothérapie APAVAC®- Recul et efficacité clinique démontrée
- Personnalisée et adaptée à l'évolution de la pathologie
- Accessible et facile à mettre en oeuvre
- Aucune toxicité pour l'animal et son entourage
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Vous aimeriez échanger à propos de l'utilisation APAVAC® sur un animal que vous soignez ?Vous souhaitez commander ?Contactez-nous par e-mail : sciences@hastim.fr ou par téléphone : 05 34 47 86 10 |
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