Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs

Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs Publisher Pubmed

Nejatollahi F¹ ; Nadimi E¹ ; Noorafshan A² ; Moazen S³ ; Alizadeh AM⁴ ; Khalighfard S⁴ ; Sahebkar A⁵

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1. Recombinant Antibody Laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran
2. Department of Neuroscience, City University in Canada, Vancouver, BC, Canada
3. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada
4. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran
5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Source: Current Protein and Peptide Science Published:2024

Abstract

Purpose: We aimed to assess the effects of a cocktail comprising three specific anti-HER2 scFvs on breast tumor formation in a xenograft mouse model and to evaluate quantitative changes in the tumor using stereological analysis. Methods: Three specific anti-HER2 phage antibodies were produced from a scFv-library using phage display technology. The cell binding capacities of the antibodies were assessed via FACS analysis. Soluble forms of the antibodies were prepared by infecting HB2151-E. coli cells and purified using a centrifugal ultrafiltration method. The purification process was evaluated by SDS-PAGE analysis. Two forms of scFv cocktails were prepared, soluble scFv and phage-scFv cocktail, which contained an equal amount/phage of each of the three antibodies. Inbred female BALB/c mice were pretreated with 5 and 20 mg/kg of the soluble scFv cocktail and 1011 phage-scFv cock-tail/kg. The mice were then injected with 2×106 SKBR-3 human breast cancer cells. Total tumor, inflammatory and non-inflammatory volumes were estimated using the Cavalieri principle after preparing photomicrograph slides. Results: The anti-HER2 scFvs showed significantly higher binding to SKBR-3 cells compared to the isotype control. SDS-PAGE analysis confirmed the high purification of the scFvs. Stereological analysis revealed that the group pretreated with 20 mg/kg of the soluble scFv cocktail exhibited the highest reductions in total tumor volume, non-inflammatory volume, and inflammatory volume, with reductions of 73%, 78%, and 72%, respectively, compared to PBS-pretreated mice (P-value < 0.0001). The volumetric ratio of necrotic tissue to total tumor volume increased by 2.2-fold and 2-fold in the 20 mg/kg of soluble scFv cocktail and phage-scFv cocktail groups, respectively, compared to the PBS-treated mice (P-value < 0.05). Conclusion: Pre-treatment with a 20 mg/kg anti-HER2 scFv cocktail resulted in a significant re-duction in tumor volume and increased necrotic area in a human breast cancer xenograft model, indicating the remarkable anti-tumor effect of the cocktail in vivo. © 2024 Bentham Science Publishers.

Style	Citing Format
MLA	Nejatollahi F, et al.. "Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs." Current Protein and Peptide Science, vol. 25, no. 5, 2024, pp. 409-418.
APA	Nejatollahi F, Nadimi E, Noorafshan A, Moazen S, Alizadeh AM, Khalighfard S, Sahebkar A (2024). Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs. Current Protein and Peptide Science, 25(5), 409-418.
Chicago	Nejatollahi F, Nadimi E, Noorafshan A, Moazen S, Alizadeh AM, Khalighfard S, Sahebkar A. "Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs." Current Protein and Peptide Science 25, no. 5 (2024): 409-418.
Harvard	Nejatollahi F et al. (2024) 'Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs', Current Protein and Peptide Science, 25(5), pp. 409-418.
Vancouver	Nejatollahi F, Nadimi E, Noorafshan A, Moazen S, Alizadeh AM, Khalighfard S, et al.. Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs. Current Protein and Peptide Science. 2024;25(5):409-418.
BibTex	@article{ author = {Nejatollahi F and Nadimi E and Noorafshan A and Moazen S and Alizadeh AM and Khalighfard S and Sahebkar A}, title = {Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs}, journal = {Current Protein and Peptide Science}, volume = {25}, number = {5}, pages = {409-418}, year = {2024} }
RIS	TY - JOUR AU - Nejatollahi F AU - Nadimi E AU - Noorafshan A AU - Moazen S AU - Alizadeh AM AU - Khalighfard S AU - Sahebkar A TI - Reduced Tumor Volume and Increased Necrosis of Human Breast Tumor Xenograft in Mice Pretreated by a Cocktail of Three Specific Anti-Her2 Scfvs JO - Current Protein and Peptide Science VL - 25 IS - 5 SP - 409 EP - 418 PY - 2024 ER -

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