Designing Cancer Vaccine Against Lung Cancer

1686 words - 7 pages

Lung cancer is a leading cause of death worldwide both in men and women. It accounts for nearly 1.2 million deaths per year. Over the last few years many advances have been made in the field of surgery, chemotherapy and radiations for treating this deadly cancer but they are unlikely to result in cure. Lung cancer is associated with very bad prognosis. So there is a dire need of developing novel therapeutic vaccines for improving prognosis of this disease
Cancer therapeutic vaccines are designed to regulate the host tumour interactions in order to shift the balance from tumour acceptance to tumour control. Therapeutic vaccine target tumour associated antigen including cancer testis antigens.
KK-LC-1, antigenic peptide is used in a Multipeptide Vaccine to target Non-small cell lung carcinoma. KK-LC-1 is designated as Kita-kyushu lung cancer antigen 1. This antigen has been recently recognized and was found to be present in approximately 40 per cent of people suffering from lung adenocarcinoma. KK-LC-1 belongs to a family of Cancer testis antigens which are expressed in many cancerous tissues but are silent in normal tissue except testis. This antigen is specifically expressed in large proportion of lung cancer tissues and not in normal tissues except testis so it should be a potential target for immunotherapy.
Use of KK-LC-1 antigenic peptide in peptide vaccine can prove to be useful in treating non-small cell lung carcinoma which accounts for 85% of lung cancers. Peptide vaccines specifically target single epitope. They are safe, non-toxic and easy to formulate. Apart from this peptide possess good tumour- penetrating ability and are biocompatible.
Antigenic peptides are determined by using bioinformatics tools BLAST and syfpeithi.
Firstly this FASTA sequence is used and BLAST search is performed
>sp|Q5H943|KKLC1_HUMAN Kita-kyushu lung cancer antigen 1 OS=Homo sapiens GN=KKLC1 PE=1 SV=1
MNFYLLLASSILCALIVFWKYRRFQRNTGEMSSNSTALALVRPSSSGLINSNTDNNLAVY
DLSRDILNNFPHSIARQKRILVNLSMVENKLVELEHTLLSKGFRGASPHRKST

BLAST is used for assuring the sequence similarity and the one with 100 % sequence similarity is picked up and the sequence is
>gi|63025190|ref|NP_001017978.1|:1-113 kita-kyushu lung cancer antigen 1 [Homo sapiens]
MNFYLLLASSILCALIVFWKYRRFQRNTGEMSSNSTALALVRPSSSGLINSNTDNNLAVYDLSRDILNNFPHSIARQKRILVNLSMVENKLVELEHTLLSKGFRGASPHRKST
Then this sequence is used in syfpeithi to predict the epitopes. Moderate affinity peptide sequence is chosen as low affinity peptides are poorly expressed and the ones with high affinity are likely to be deleted in thymus.



Peptides marked in blue arrows are chosen for this vaccine as they represent moderate affinity. Nanomers are for MHC1 and 15 mers are for MHCII. This multipeptide vaccine offers an advantage that if one epitope fails to elicit immune response other epitope can.
Ultimate aim of the peptide vaccine is to activate the components of immune system T lymphocytes as these cells are responsible for...

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