Preprint Article Version 1 This version is not peer-reviewed

Grapefruit-derived vesicles loaded with recombinant HSP70 activate antitumor immunity in colon cancer in vitro and in vivo

Version 1 : Received: 28 October 2024 / Approved: 29 October 2024 / Online: 29 October 2024 (09:47:19 CET)

How to cite: Garaeva, L.; Komarova, E.; Emelianova, S.; Putevich, E.; Konevega, A. L.; Margulis, B.; Guzhova, I.; Shtam, T. Grapefruit-derived vesicles loaded with recombinant HSP70 activate antitumor immunity in colon cancer in vitro and in vivo. Preprints 2024, 2024102254. https://doi.org/10.20944/preprints202410.2254.v1 Garaeva, L.; Komarova, E.; Emelianova, S.; Putevich, E.; Konevega, A. L.; Margulis, B.; Guzhova, I.; Shtam, T. Grapefruit-derived vesicles loaded with recombinant HSP70 activate antitumor immunity in colon cancer in vitro and in vivo. Preprints 2024, 2024102254. https://doi.org/10.20944/preprints202410.2254.v1

Abstract

Stress protein HSP70 administered exogenously demonstrated high potential as efficient adjuvant in anti-tumor immune response. To enhance the antigen-presenting activity and stability of pure HSP70 we suggest here its incorporation in nanometer vesicles made of plant juice. Earlier we found such packing in grapefruit-derived extracellular vesicles (GEV) was able to store the protein with no loss of its major function, chaperonic activity. To check whether HSP70 in composition of GEV can elicit immune response we purified the vesicles, loaded them with recombinant human HSP70 (GEV-HSP70) and after characterization of the protein quantity and activity injected in Balb/c mice with growing CT-26 colon carcinoma tumor. The injections course reduced the tumor growth rate by 40% and expand the life span by 50%; the effect was corroborated with lowering of TGF-b1 and Il-10 levels in blood; this is comparable to the effect of soluble HSP70 with a concentration 25 times higher than that of GEV-HSP70. In vitro analysis of immunomodulatory activity of GEV-HSP70 showed that anti-tumor response in GEV-HSP70-treated mice was associated with the accumulation of CD8+ cells. These results demonstrate high feasibility and efficacy of novel HSP70-based technique in activation of the specific response to colon tumors.

Keywords

HSP70; extracellular vesicles; plant-derived extracellular vesicles; drug delivery systems; antitumor immunity; colon cancer

Subject

Biology and Life Sciences, Biology and Biotechnology

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