Personalised Cancer Vaccines

How Personalised mRNA Cancer Vaccines Work

Eight steps from computation to clinic, tumour biopsy through to immune monitoring.

Step 1

Tumour Biopsy & Normal Tissue

A tissue sample is collected from the patient's tumour alongside a matched normal tissue sample to serve as a germline reference.

Core needle or surgical excision biopsy

Matched peripheral blood mononuclear cells collected

Tissue preserved for DNA and RNA extraction

Step 2

Whole-Exome & RNA Sequencing

DNA from both tumour and normal samples undergoes whole-exome sequencing to identify somatic mutations. RNA sequencing confirms which mutated genes are actively expressed.

Whole-exome sequencing at ~200x depth

Tumour RNA-seq to verify expression of mutant alleles

Somatic variant calling against germline reference

Step 3

Neoantigen Prediction & Selection

Bioinformatic pipelines predict which somatic mutations generate novel peptides (neoantigens) that will be presented by the patient's own HLA molecules and recognised by T cells.

HLA typing from germline sequencing data

MHC-I and MHC-II binding affinity prediction

Top 10-20 neoantigens ranked and selected

Step 4

mRNA Construct Design

A synthetic mRNA sequence is designed encoding a polyepitope cassette containing multiple neoantigen peptides joined by linker sequences, flanked by optimised UTRs and a poly(A) tail.

Neoantigen epitopes arranged in a polyepitope string

Codon optimisation and modified nucleosides (e.g. N1-methylpseudouridine)

5' cap, optimised UTRs, and poly(A) tail incorporated

Step 5

mRNA Synthesis & LNP Encapsulation

The designed sequence is synthesised by in vitro transcription then encapsulated in lipid nanoparticles to protect it from degradation and enable cellular uptake.

In vitro transcription using T7 RNA polymerase

Enzymatic capping and purification (HPLC or cellulose)

Microfluidic mixing into ionisable lipid nanoparticles

Step 6

Quality Control & Release Testing

The formulated vaccine undergoes rigorous quality testing to confirm identity, purity, and potency before release.

mRNA integrity assessed by capillary electrophoresis

LNP size, polydispersity, and encapsulation efficiency measured

Endotoxin testing

Release spec

Step 7

Patient Administration

The personalised vaccine is administered to the patient, typically as a series of injections, often combined with immune checkpoint inhibitors.

Priming dose followed by boost injections

Often combined with anti-PD-1 or anti-PD-L1 therapy

Administered intravenously or intramuscularly

Step 8

Immune Monitoring & Response

The patient's immune response is monitored to confirm neoantigen-specific T cell activation. Circulating tumour DNA and imaging assess clinical response.

ELISpot and multimer staining for neoantigen-specific T cells

Circulating tumour DNA (ctDNA) tracking for molecular response

Radiographic imaging to assess tumour regression

Neoantigen Discovery

Computational analysis of tumour genome sequencing data to identify and prioritise neoantigens. Machine learning approaches predict which mutations will generate effective immune responses, validated through T-cell assays.

mRNA Manufacture, personalised mRNA vaccine design and synthesis

mRNA Vaccine Design & Manufacture

Rapid design and synthesis using optimised codon design, nucleotide modifications and lipid nanoparticle formulation. Manufactured in as little as 2-3 weeks from synthetic DNA templates.

Preclinical Evaluation

In vitro and in vivo evaluation of mRNA vaccine candidates across multiple cancer models. Progression of promising candidates toward Phase-I clinical trials through our clinical manufacturing capabilities.

The Neo-Antigen Approach