Plate 09a — Procedure
A product is made for one single tumour — one that exists for this one person and nobody else.
What it costs today
Today this route costs money and needs a laboratory, a physician and an institution that says yes. What we want is for it to be open one day to anyone who needs it, not only to whoever can pay for it.
The first four stages exist only inside a trial.
01
Send a blood sample and a sample of the tumour to a laboratory.
Tumour biopsy with a paired germline sample
How it is done
Fresh tissue from a biopsy, or material kept from an earlier operation. The blood is not an extra, it is the reference: without your own inherited sequence there is no way to tell which changes the tumour made and which you have carried since birth.
Who does it
The treating clinic takes both and sends them on.
02
The tumour's DNA is sequenced piece by piece.
Tumour and germline exome or genome sequencing
How it is done
The two samples are sequenced separately and subtracted from one another. What is left is what exists only in the tumour — typically a few dozen to a few hundred changes that alter a protein. Everything that follows works on that remainder alone.
Who does it
A sequencing laboratory, on the clinic's order.
03
Software and AI look for the tumour's identifying marks and weak points.
Neoantigen prediction and ranking
How it is done
Not every mutation is visible. For each one it is predicted whether the altered fragment is presented on the cell surface at all, and whether T cells could bind to it. Hundreds become dozens: the mRNA-4157 construct, for one, carries up to 34 of them.
Who does it
The manufacturer, or an academic consortium.
04
AlphaFold and similar programs test the possible effect and the dangers.
Construct design with structure prediction
How it is done
The selected fragments are encoded into a single construct. Binding prediction does the choosing; structure prediction — AlphaFold and related methods — checks whether a fragment really sits in the binding groove before anything is manufactured. Checking on a computer is what turned years into months.
Who does it
The same group, before manufacture begins.
05
The application goes to the regulator (FDA).
IND application, or enrolment under an existing one
How it is done
Inside a trial this runs under the authorisation the trial already holds and you never see it. Outside one, your physician has to become a sponsor-investigator and file it — regulators now publish specific guidance for individualised products, so the path exists on paper.
Who does it
A physician, who becomes responsible for it. Never the patient.
What this drawing is not
None of these stages can be bought or booked. Four of them exist only inside a trial you have to be admitted to, and the fifth is the step almost every attempt stops at. This describes how it works when it works — not how often it does.
Five stages. The first four require that someone has been admitted to a trial. The fifth is the case where no trial fits: then the application to the regulator has to be filed directly.
This section is information, not advertising. It describes routes that exist, names no provider, recommends no treatment and promises no outcome. Nothing here replaces a conversation with a doctor.
Where this procedure sits
Neoantigen therapy is one of seven routes that exist once standard treatment has failed. Which they are, and what each one requires, is on the routes page.
Figures
Expanded access: 692 of 692 single-patient oncology applications allowed to proceed, median processing time one day (FDA Project Facilitate). Individualised neoantigen therapy mRNA-4157/V940 with pembrolizumab: 49% lower risk of recurrence or death than pembrolizumab alone at five years — in resected, high-risk melanoma (KEYNOTE-942, phase 2b). That is an early-stage, post-surgical setting and not the situation this page describes. N-of-1 development: ten months from diagnosis to first dose in the milasen case (NEJM 2019) — Batten disease, not cancer.