In silico proteomic characterization of human epidermal growth factor receptor 2 (HER-2) for the mapping of high affinity antigenic determinants against breast cancer

被引:19
作者
Baloria, Urvashi [2 ]
Akhoon, Bashir Akhlaq [1 ,2 ]
Gupta, Shishir Kumar
Sharma, Sujata [3 ]
Verma, Vijeshwar [2 ]
机构
[1] BIF Ctr, Sch Biotechnol, Katra 182320, Jammu And Kahmi, India
[2] Shri Mata Vaishno Devi SMVD Univ, Ctr Bioinformat, Sch Biotechnol, Jammu 182320, Jammu And Kahmi, India
[3] IIIM, Jammu 180001, Jammu And Kahmi, India
关键词
HER-2; Antigenic determinants; Computational screening; DNA vaccine; Breast cancer; METHYLCHOLANTHRENE-INDUCED SARCOMAS; DENDRITIC CELL DYSFUNCTION; T-CELL; EPITOPE PREDICTION; ANTITUMOR IMMUNITY; DNA VACCINES; PROGNOSTIC-FACTORS; PROTEIN; ANTIBODY; CARCINOMA;
D O I
10.1007/s00726-010-0830-x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
Multiple different approaches are being used to activate the immune system against breast cancer. Vaccine therapy in general follows the principle that injections of various substances ultimately result in the presentation of tumor peptides to the patient's immune system. We proposed a potential in silico DNA vaccine against breast cancer by integrating high affinity T cell (MHC-I and MHC-II) and B cell (continuous and discontinuous) epitopes. The matching of the HLA haplotype and antigen was performed to provide the appropriate peptide epitope suitable for majority of the patients. The immunogenic nature of the antigenic construct was also enhanced by the administration of consensus epitopes. The potency of DNA vaccines depends on the efficient expression and presentation of the encoded antigen of interest and the chances of efficient expression of our antigenic construct in host organism was also verified by in silico approaches. An attempt was made to overcome the limited potency of the DNA vaccine by targeting DNA to professional antigen-presenting cells (APCs). A higher immune response theoretically corresponds to a higher survival rate of patients. Therefore, optimization studies were also employed to enhance the immunogenicity of proposed in silico DNA vaccine.
引用
收藏
页码:1349 / 1360
页数:12
相关论文
共 79 条
[1]
In silico designing and optimization of anti-breast cancer antibody mimetic oligopeptide targeting HER-2 in women [J].
Akhoon, Bashir A. ;
Gupta, Shishir K. ;
Verma, Vijeshwar ;
Dhaliwal, Gagan ;
Srivastava, Mugdha ;
Gupta, Shailendra K. ;
Ahmad, Raja Feroz .
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2010, 28 (07) :664-669
[2]
Prediction of residues in discontinuous B-cell epitopes using protein 3D structures [J].
Andersen, Pernille Haste ;
Nielsen, Morten ;
Lund, Ole .
PROTEIN SCIENCE, 2006, 15 (11) :2558-2567
[3]
Immune responses to all ErbB family receptors detectable in serum of cancer patients [J].
Bei, R ;
Masuelli, L ;
Moriconi, E ;
Visco, V ;
Moretti, A ;
Kraus, MH ;
Muraro, R .
ONCOGENE, 1999, 18 (06) :1267-1275
[4]
Benchmarking B cell epitope prediction: Underperformance of existing methods [J].
Blythe, MJ ;
Flower, DR .
PROTEIN SCIENCE, 2005, 14 (01) :246-248
[5]
Defining putative T cell epitopes from PE and PPE families of proteins of Mycobacterium tuberculosis with vaccine potential [J].
Chaitra, MG ;
Hariharaputran, S ;
Chandra, NR ;
Shaila, MS ;
Nayak, R .
VACCINE, 2005, 23 (10) :1265-1272
[6]
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab [J].
Cho, HS ;
Mason, K ;
Ramyar, KX ;
Stanley, AM ;
Gabelli, SB ;
Denney, DW ;
Leahy, DJ .
NATURE, 2003, 421 (6924) :756-760
[7]
CANONICAL STRUCTURES FOR THE HYPERVARIABLE REGIONS OF IMMUNOGLOBULINS [J].
CHOTHIA, C ;
LESK, AM .
JOURNAL OF MOLECULAR BIOLOGY, 1987, 196 (04) :901-917
[8]
Amplification and overexpression of HER2/neu gene and HER2/neu protein in salivary duct carcinoma of the parotid gland [J].
Cornolti, Giorgio ;
Ungari, Marco ;
Morassi, Maria Laura ;
Facchetti, Fabio ;
Rossi, Elisa ;
Lombardi, Davide ;
Nicolai, Piero .
ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 2007, 133 (10) :1031-1036
[9]
Reducing risk, improving outcomes: Bioengineering less immunogenic protein therapeutics [J].
De Groot, Anne S. ;
Martin, William .
CLINICAL IMMUNOLOGY, 2009, 131 (02) :189-201
[10]
Immunomics: discovering new targets for vaccines and therapeutics [J].
De Groot, AS .
DRUG DISCOVERY TODAY, 2006, 11 (5-6) :203-209