Cancer VAC to combat lynchOctober 10, 2018
Arecent study by Bengaluru-based genetics research and diagnostics player MedGenome has found that a cancer vaccine would be the answer for personalized treatment for Lynch Syndrome (LS), a hereditary non-polyposis colorectal cancer (HNPCC).
Lynch Syndrome, one of the most common hereditary syndromes, increases the lifetime risk of developing cancers of other organs, such as colon, stomach, small intestines, liver, kidney, uterus, brain, pelvis and prostate.
MedGenome, in collaboration with Kailash Cancer Hospital and Research Center (KCHRC), Goraj, examined the feasibility of treating Lynch Syndrome using a personalized cancer vaccine approach by identifying potential immunogenic tumour specific alterations.
The company used its proprietary neoepitope prioritization pipeline – OncoPeptVAC – to select potential immunogenic peptides from whole-exome and RNA-seq data generated from patient tumour. From a list of over 50 predicted neoepitopes, three neoepitopes were tested in an ex vivo CD8+ T cell activation assay confirming their immunogenicity.
Explaining the working of this potential vaccine treatment, Amit Chaudhuri, Vice-President, R&D at MedGenome, said since cancer mutations are recognized by the body’s immune system as foreign, tumour cells carrying these mutations are often eliminated. So, it is often very challenging to predict which mutations are potentially immunogenic. The answer to such challenging conditions are good cancer vaccines.
MedGenome has built a bioinformatic pipeline to predict potential cancer vaccines by analysing a patient’s tumour using next generation sequencing. The process involves sequencing tumour DNA to identify all cancer mutations, using RNA sequencing data to ascertain the mutations that are expressed by the tumour cells, and analysing the properties of the mutated amino acid to predict whether it will be recognized by the T cell receptor.
In the lynch syndrome study, the patient’s tumour contained over 900 cancer mutations, of which about 50 were predicted to be immunogenic – which means that these mutations or neoepitopes were predicted to be recognized by the T cells to mount an immune response. Three predicted neoepitopes were tested in an assay and were found to activate T cells, validating that the prediction was correct. These three neoepitopes can be used as vaccines for treating the patient. It is likely that many of the 50 predicted epitopes will also be immunogenic, although it was not tested in the experiment. The assay is time consuming, laborious and requires specialized skill-sets to perform.
According to Dr. Rakshit Shah, surgical oncologist, KCHRC, Vadodara, the screening for genetic mutation in colorectal cancer patients, especially those with a familial history, could help in identifying those that are vulnerable to the disease.
“Such genetic-based screening could be an efficient way of preventing colorectal cancer. Families with history of colorectal cancer like Lynch syndrome should be advised to undergo genetic screening and if they carry mutations like MLH1, they are likely to develop the disease before the age of 50. “Our study is unique, as genetic screening in familial colorectal cancer has not been widely reported in India,” he added.
“Given that Lynch syndrome has limited treatment options, this study provides a basis for considering a cancer vaccine approach that could be used either as monotherapy or in combination with established immuno-oncology or chemotherapy drugs,” said Dr. Amit Chaudhuri, who co-authored the study.
Talking about the potential development of the vaccine, Dr Chaudhuri added that the company’s pipeline is the front-end of a long chain of processes that will lead to a product that can be given to the patient. “A big challenge is GMP manufacturing of peptides for individual patients, and formulating the peptides with appropriate adjuvants so that the vaccines can evoke a strong immune response in the patient.,” he added.