Personalized Cancer Vaccines – first clinical case in progress

NeoScreen®: Selecting neo-epitopes for a personalized cancer vaccine – First clinical case in progress

NeoScreen® from Immunitrack is a leading platform technology for the study of Major Histocompatibility Complex class I and class II (MHC I & II) interactions with potential tumour-specific epitopes.

Immunitrack is reporting its first case of neo-epitope selection for the treatment of a patient suffering from colorectal cancer. To our knowledge this is the first case where in-silico methods are combined with in vitro MHC/neo-epitope binding assay in a fully personalized manner – and in less than 3 weeks!

The patient is expected to be treated in May 2019.

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A Case Study

1. Cancer mutation detection though analysis of data from whole exome sequencing

One patient, suffering from colorectal cancer, had whole exome sequencing (WES) performed on 2 tumor biopsies.

More than 20,000 mutations were identified through variant calling: here DNA from patient is compared to a reference DNA. Variants in normal DNA is ok, while variants unique to tumor is not ok. Somatic missense (change at protein level) and frameshift mutations analysed for predicted affinity using proprietary AI platform.

100 most likely binders per patient specific MHC were predicted. A total of 8 MHC alleles (for MHC I, A*0101, A*2402, B*1301, B*3501, C*0401, C*0702; and MHC II, DRB1*0401, DRB1*1501). In total, some 800 potential neo-epitopes were selected for further analysis.

Whole Exome Sequencing (WES) performed on 2 cancer biopsies and a blood sample.

More than 20,000 mutations were identified through variant calling.

Around 800 neo-eptiopes selected as high affinity binders to patient MHC I & II.

 

2. Selection of most stable epitopes by NeoScreen®

Stability assay measurement using NeoScreen® performed on all 800 epitopes:
In this setup, MHC complexes are stressed using various concentrations of UREA. All analysis are conducted in high throughput using liquid handlers to distribute samples on 384 well plates and readouts are obtained on the envision system from Perkin Elmer.

Here, a total of approximately 200 peptides were determined as highly stable when compared to reference peptides.

Perform MHC/epitope stability measurement of 100 peptides with highest predicted affinity pr. allele.

6 MHC I and 2 MHC II patient specific alleles analysed

Binding assay performed to select neo-peptides with high stability

3. Further selection criteria of neo-epitopes

A further filter based on mutations likelihood of expression (house hold genes), allowed us to reduce the number of neo-epitopes included in the vaccine to 32.

All the activities depicted were performed in less than 3 weeks.
The patient is expected to be treated in May 2019.

200 most stable neo-epitopes are further filtered down to 32 according to global tissue expression.

Final selection of 32 neo-epitopes for a personalized cancer vaccine

NeoScreen®
The ultimate design of personalized cancer vaccines

NeoScreen® allows Immunitrack to rapidly screen libraries containing thousands of (neo)epitopes. Depending on the desired immune response, our clients can then pick the best candidates for taking forward, for example in therapeutic development projects. Epitopes from viruses, bacteria, but also from biologics, vaccines and cancer cells, may be presented by MHC class I (for somatic cells) and MHC II (for antigen presenting cells).

Other area of application: De-immunization of biologics, development of vaccine, biomarkers.