FM OCTOBER 2018 ISSUE - digital edition

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CANCER VAC TO COMBAT LYNCH
Indian researchers discover that a personalised vaccine could well address a
hereditary form of colorectal cancer
A
recent 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 nonpolyposis
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 wholeexome
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
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.
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 immunooncology
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.
12 / FUTURE MEDICINE / OCTOBER 2018