Potent anti-tumor immune response and tumor growth inhibition induced by HER2 subdomain fusion protein in a mouse tumor model

Ghaedi, Mojgan; Golsaz‐Shirazi, Forough; Bahadori, Tannaz; Khoshnoodi, Jalal; Mortezagholi, Sahar; Jeddi‐Tehrani, Mahmood; Amiri, Mohammad Mehdi; Shokri, Fazel

doi:10.1007/s00432-022-04084-0

Cited by 2 publications

(3 citation statements)

References 68 publications

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“…The results revealed that both adjuvants have similar effect in stimulating ROR1-specific humoral and cellular mediated immunity ( Figure 2 and Figure 3 ). This finding does not support our recent data, showing superiority of CpG over other adjuvants such as Freund’s, Montanide and Alum in a HER2 positive mouse tumor model [ 40 ]. This discrepancy might be due to the presence of Fc fragment in our H17 fusion protein which may strength the anti-tumor response to a level that superiority of the CpG adjuvant is no longer observed [ 18 , 19 , 41 ].…”

Section: Discussioncontrasting

confidence: 98%

“…This discrepancy might be due to the presence of Fc fragment in our H17 fusion protein which may strength the anti-tumor response to a level that superiority of the CpG adjuvant is no longer observed [ 18 , 19 , 41 ]. The type of the tumor may also contribute to this discrepancy because in the present study we employed syngeneic ROR1-expressing mouse colon and breast cancer cell lines, whereas in our previous study HER2-expressing rat breast tumor cell line was used [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

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Preclinical Assessment of Immunogenicity and Protectivity of Novel ROR1 Fusion Proteins in a Mouse Tumor Model

Hassannia

Amiri

Ghaedi

et al. 2022

Cancers

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The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a new tumor associated antigen (TAA) which is overexpressed in several hematopoietic and solid malignancies. The present study aimed to produce and evaluate different fusion proteins of mouse ROR1 (mROR1) to enhance immunogenicity and protective efficacy of ROR1. Four ROR1 fusion proteins composed of extracellular region of mROR1, immunogenic fragments of TT as well as Fc region of mouse IgG2a were produced and employed to immunize Balb/C mice. Humoral and cellular immune responses and anti-tumor effects of these fusion proteins were evaluated using two different syngeneic murine ROR1+ tumor models. ROR1-specific antibodies were induced in all groups of mice. The levels of IFN-γ, IL-17 and IL-22 cytokines in culture supernatants of stimulated splenocytes were increased in all groups of immunized mice, particularly mice immunized with TT-mROR1-Fc fusion proteins. The frequency of ROR1-specific CTLs was higher in mice immunized with TT-mROR1-Fc fusion proteins. Finally, results of tumor challenge in immunized mice showed that immunization with TT-mROR1-Fc fusion proteins completely inhibited ROR1+ tumor cells growth in two different syngeneic tumor models until day 120 post tumor challenge. Our preclinical findings, for the first time, showed that our fusion proteins could be considered as a potential candidate vaccine for active immunotherapy of ROR1-expressing malignancies.

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Section: Discussioncontrasting

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Preclinical Assessment of Immunogenicity and Protectivity of Novel ROR1 Fusion Proteins in a Mouse Tumor Model

Hassannia

Amiri

Ghaedi

et al. 2022

Cancers

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“…The gene encoding the Fc region of human IgG1 without hinge sequence (GenBank accession number: NC_000014.9) was fused at the N-terminal to the gene encoding SARS-CoV-2 RBD (Wuhan Hu1; GenBank accession number: MN908947) and then inserted into a homemade dual promoter expression plasmid that contains glutamine synthetase (GS) as a selection marker [16,17]. The plasmid containing RBD-Fc was transfected into CHO-K1 cells using Lipofectamine 3000 reagent (Life Technologies, USA).…”

Section: Protein Expression and Purificationmentioning

confidence: 99%

Preclinical assessment of a recombinant RBD-Fc fusion protein as SARS-CoV-2 candidate vaccine

Dashti,

Golsaz-Shirazi,

Soltanghoraee

et al. 2024

EuJMI

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BackgroundWaning immunity and emergence of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlight the need for further research in vaccine development.MethodsA recombinant fusion protein containing the receptor-binding domain (RBD) fused to the human IgG1 Fc (RBD-Fc) was produced in CHO-K1 cells. RBD-Fc was emulsified with four adjuvants to evaluate its immunogenicity. The RBD-specific humoral and cellular immune responses were assessed by ELISA. The virus neutralizing potency of the vaccine was investigated using four neutralization methods. Safety was studied in mice and rabbits, and Antibody-Dependent Enhancement (ADE) effects were investigated by flow cytometry.ResultsRBD-Fc emulsified in Alum induced a high titer of anti-RBD antibodies with remarkable efficacy in neutralizing both pseudotyped and live SARS-CoV-2 Delta variant. The neutralization potency dropped significantly in response to the Omicron variant. RBD-Fc induced both TH2 and particularly TH1 immune responses. Histopathologic examinations demonstrated no substantial pathologic changes in different organs. No changes in serum biochemical and hematologic parameters were observed. ADE effect was not observed following immunization with RBD-Fc.ConclusionRBD-Fc elicits highly robust neutralizing antibodies and cellular immune responses, with no adverse effects. Therefore, it could be considered a promising and safe subunit vaccine against SARS-CoV-2.

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Potent anti-tumor immune response and tumor growth inhibition induced by HER2 subdomain fusion protein in a mouse tumor model

Cited by 2 publications

References 68 publications

Preclinical Assessment of Immunogenicity and Protectivity of Novel ROR1 Fusion Proteins in a Mouse Tumor Model

Preclinical Assessment of Immunogenicity and Protectivity of Novel ROR1 Fusion Proteins in a Mouse Tumor Model

Preclinical assessment of a recombinant RBD-Fc fusion protein as SARS-CoV-2 candidate vaccine

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