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An In silico Chimeric Vaccine Targeting Breast Cancer Containing Inherent Adjuvant.

Imani Fooladi AA, Mahmoodzadeh Hosseini H, Amani J - Iran J Cancer Prev (2015)

Bottom Line: We hypothesized the extracellular domain of receptor tyrosine kinase like orphan receptor 1 (ROR-1) along with a super antigen such as staphylococcal enterotoxin B could be a potent vaccine for drug resistant breast cancer.Here, we assessed the findings of bioinformatics analysis to identify the antitumor immune properties of this chimeric construct.Our result suggested that chimeric model is capable to be a stimulant of both T-cell and B- cell mediated immune responses with an acceptable accessibility and solubility but without any allergenicity.

View Article: PubMed Central - PubMed

Affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran.

ABSTRACT

Background: Today, Lack of efficient therapeutic strategy for breast cancer (the most common cause of death in women) is one of the momentous problematic topics for all health care committees. Designing new specific vaccine, based on antigens located on the surface of cancer cells can be useful. Over expression of ROR1, lacked of HER2/neu, and hormone receptors on cell surface in the breast cancer, introduce this protein as an appropriate candidate for designing cancer vaccine.

Objectives: We hypothesized the extracellular domain of receptor tyrosine kinase like orphan receptor 1 (ROR-1) along with a super antigen such as staphylococcal enterotoxin B could be a potent vaccine for drug resistant breast cancer.

Materials and methods: Here, we assessed the findings of bioinformatics analysis to identify the antitumor immune properties of this chimeric construct. In addition, the stability, physic-chemical properties and allergic potency of designed fusion protein were investigated by valid bioinformatics software.

Results: Our result suggested that chimeric model is capable to be a stimulant of both T-cell and B- cell mediated immune responses with an acceptable accessibility and solubility but without any allergenicity.

Conclusions: The ROR-1 with an enterotoxin B could be a potent vaccine for breast cancer.

No MeSH data available.


Related in: MedlinePlus

A Probabilistic Structural Model for Chimeric Protein Using I-TASSER SoftwareAs illustrate in figure two domains of Ror1 (in the left site) separate with the linker from SEB fragment (in the right site).
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A2326FIG3: A Probabilistic Structural Model for Chimeric Protein Using I-TASSER SoftwareAs illustrate in figure two domains of Ror1 (in the left site) separate with the linker from SEB fragment (in the right site).

Mentions: As findings from I-TASSER server, five three-dimensional models were afforded for our designed protein fusing with GSGGSGGSGGSG as a linker. Figure 3 illustrates the best tertiary model predicted for describing protein, which has three separate parts and two domains. The confidence score, as a factor estimates the quality of suggested model was -2.22. What’s more, the expected TM- score and RMSD were 10.9 ± 4.6 Å and 0.53 ± 0.15, respectively. Additionally, we fused two proteins using (HDPVRVS) 2 as an alternative construct. I-TASSER results from predicting tertiary models for this alternative construct showed no appropriate structure therefore we exerted all our analysis only on the first construct. The Ramachandran plot assessment viewed that 80.2% (413 amino acids), 11.1% (57 amino acids) and 8.7% (45 amino acids) were situated in the favored region, allowed region and outlier region, respectively (Figure 4). The quality assessment of the Ramachandran plot revealed that more than 90% of residues located on acceptable (favored and allowed) regions. In accordance with Pdb Viewer analysis, the energy minimization amount was -9536.065 Kcal/mol that portended the plausible stability for our designed construct.


An In silico Chimeric Vaccine Targeting Breast Cancer Containing Inherent Adjuvant.

Imani Fooladi AA, Mahmoodzadeh Hosseini H, Amani J - Iran J Cancer Prev (2015)

A Probabilistic Structural Model for Chimeric Protein Using I-TASSER SoftwareAs illustrate in figure two domains of Ror1 (in the left site) separate with the linker from SEB fragment (in the right site).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581362&req=5

A2326FIG3: A Probabilistic Structural Model for Chimeric Protein Using I-TASSER SoftwareAs illustrate in figure two domains of Ror1 (in the left site) separate with the linker from SEB fragment (in the right site).
Mentions: As findings from I-TASSER server, five three-dimensional models were afforded for our designed protein fusing with GSGGSGGSGGSG as a linker. Figure 3 illustrates the best tertiary model predicted for describing protein, which has three separate parts and two domains. The confidence score, as a factor estimates the quality of suggested model was -2.22. What’s more, the expected TM- score and RMSD were 10.9 ± 4.6 Å and 0.53 ± 0.15, respectively. Additionally, we fused two proteins using (HDPVRVS) 2 as an alternative construct. I-TASSER results from predicting tertiary models for this alternative construct showed no appropriate structure therefore we exerted all our analysis only on the first construct. The Ramachandran plot assessment viewed that 80.2% (413 amino acids), 11.1% (57 amino acids) and 8.7% (45 amino acids) were situated in the favored region, allowed region and outlier region, respectively (Figure 4). The quality assessment of the Ramachandran plot revealed that more than 90% of residues located on acceptable (favored and allowed) regions. In accordance with Pdb Viewer analysis, the energy minimization amount was -9536.065 Kcal/mol that portended the plausible stability for our designed construct.

Bottom Line: We hypothesized the extracellular domain of receptor tyrosine kinase like orphan receptor 1 (ROR-1) along with a super antigen such as staphylococcal enterotoxin B could be a potent vaccine for drug resistant breast cancer.Here, we assessed the findings of bioinformatics analysis to identify the antitumor immune properties of this chimeric construct.Our result suggested that chimeric model is capable to be a stimulant of both T-cell and B- cell mediated immune responses with an acceptable accessibility and solubility but without any allergenicity.

View Article: PubMed Central - PubMed

Affiliation: Applied Microbiology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran.

ABSTRACT

Background: Today, Lack of efficient therapeutic strategy for breast cancer (the most common cause of death in women) is one of the momentous problematic topics for all health care committees. Designing new specific vaccine, based on antigens located on the surface of cancer cells can be useful. Over expression of ROR1, lacked of HER2/neu, and hormone receptors on cell surface in the breast cancer, introduce this protein as an appropriate candidate for designing cancer vaccine.

Objectives: We hypothesized the extracellular domain of receptor tyrosine kinase like orphan receptor 1 (ROR-1) along with a super antigen such as staphylococcal enterotoxin B could be a potent vaccine for drug resistant breast cancer.

Materials and methods: Here, we assessed the findings of bioinformatics analysis to identify the antitumor immune properties of this chimeric construct. In addition, the stability, physic-chemical properties and allergic potency of designed fusion protein were investigated by valid bioinformatics software.

Results: Our result suggested that chimeric model is capable to be a stimulant of both T-cell and B- cell mediated immune responses with an acceptable accessibility and solubility but without any allergenicity.

Conclusions: The ROR-1 with an enterotoxin B could be a potent vaccine for breast cancer.

No MeSH data available.


Related in: MedlinePlus