Trying to get my head around BNT116 cancer vaccine

Reading: Promising lung cancer vaccine trial begins in UK, BBC News, 23 August 2024.

This is like science fiction. Cancer? “Just pop this mRNA vaccine and monoclonal antibody we whipped up in the lab” (if it works).

A 67-year-old man has become the first person in the UK to try what doctors hope will be a revolutionary new treatment for lung cancer - a vaccine that tells the body how to fight and kill the disease.

In my head the word "vaccine" is associated with preventing a disease. Here it's giving the immune system the clues it needs to find and destroy an existing cancer.

The vaccine is called BNT116 and it's from BioNTech. It's an mRNA vaccine, which means it's injected, goes into a cell, and a cell goes on a produces whatever it encodes. In this case it encodes antigens expressed by a particular lung cancer—tumour associated antigens (TAA). I presume it's the mutations in the cancer that results in the antigen expression.

The effect is that the immune system learns to recognise the antigens, and can then seek and destroy cells expressing them, namely the cancer cells.

This is cool for a few reasons:

Non-small cell lung cancer (NSCLC), the cancer being targeted, is 85% of all lung cancers, so a decent target. Lung cancer generally is 11% of cancers globally, and the biggest killer accounting for 18% of cancer deaths.
In advanced form it's bad news, with a 5 year survival.
BioNTech (and presumably others) have a platform for developing these targeted vaccines. They call their platform "FixVac”

Here's how they describe FixVac:

While every patient’s tumor has a unique composition, they can share certain sets of markers, so-called antigens. These markers are consistent within specific cancer types and are often expressed in many patients with the same type of cancer but not found in healthy cells in the body. As cancer cells have developed mechanisms to avoid detection by the immune system, a big challenge in treating cancer successfully is that the immune system does not recognize the cancer cells as malignant cells and thus does not trigger an immune response to attack and defeat this enemy. By presenting the right set of antigens for each cancer indication to the immune system, we can activate immune cells that recognize cancer-specific antigens and turn them against the cancer cells. This idea is the basis for our FixVac mRNA cancer vaccine platform.

So it's a general principle, not just a single breakthrough treatment.

In terms of delivery, the trial is not one jab: there are various repeated treatments, dropping down to once every three weeks for a year.

It's going to be given in combination with cemiplimab, which is an existing monoclonal antibody. This is a PD-1 inhibitor, and PD-1 is the "Programmed Cell Death Protein 1". When PD-1 binds to a ligand, it reduces the immune response (e.g., preventing T-cell activation). Tumor cells use PD-1 to hide from the immune system: even if a T-cell shows up to kill the cancel cell, it would be stopped. So it makes sense to combine the vaccine with cemiplimab to make the whole treatment more likely to succeed.

Wow. Just wow.

Sources:

BioNTech FixVac platform page: The conception of our mRNA platforms.
PD-1 inhibitors: Immune Checkpoint Inhibitors and Their Side Effects.
UCL Hospitals press release: First UK lung cancer patient receives novel immune therapy at UCLH.

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