In-situ cancer vaccine knocks out lymphoma

19 April 2019

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A new technique, termed an in-situ tumour vaccine, trains the immune system to recognise and attack cancer...

The immune system can have trouble identifying cancerous cells as a threat, because they are still the body’s own cells and can escape immune surveillance.

The new therapy, known as an “in-situ vaccine,” involves injecting a sequence of immune stimulant molecules into a tumour to attract key immune cells and activate them against markers displayed uniquely by tumour cells.

Developed by scientists at Mount Sinai School of Medicine in New York, the approach has already shown promising results in a small human clinical trial. And because the therapy uses the common properties of the immune system rather than the tumour itself, the team say it isn’t limited to one type of cancer.

The first step in the in-situ vaccine process is to inject into a tumour a molecule called Flt-3L. This is a potent signal that summons immune dendritic cells to the area. Dendritic cells are powerful "antigen presenting cells" that direct the attention of immune T cells towards specific targets. “The dendritic cell is the general of the immune army and it instructs the T cell soldiers whom to attack and eliminate,” explains Joshua Brody, lead author of the study that has been published in Nature Medicine.

Next, a small localised dose of radiotherapy is applied to the tumour. This causes some cancer cells to break apart and releases their identifying markers, known as antigens. “Those dendritic cells then gobble up the antigens so they will be able to present them to the immune soldiers, to the T-cells,” says Brody.

Lastly, another injection is given, this time of an immune stimulant molecule called a TLR or "toll-like receptor" agonist, which activates the antigen-loaded dendritic cells, which display the tumour antigens to T-cells that are capable of killing cancer cells bearing those same markers wherever they are encountered, including throughout the body.

So far the Mount Sinai team have tested the approach on 11 patients with lymphoma, a cancer of white blood cells.

“We've had some patients with partial and complete remissions of their cancers, and those remissions have been going on for months or years for some of these patients,” says Dr Brody.

The results suggest the effects can last a long time after the initial treatment, but there is the potential for a “booster vaccine” if there is still tumour present when the immune memory fades.

The team have also carried out experiments in mice combining the in-situ vaccine with other cancer drugs, called immune checkpoint inhibitors, which keep the immune reaction going for longer by blocking the signal that would eventually turn off the T-cell soldiers. Using these together with the vaccine was three times more effective than using either treatment alone.

A larger clinical trial on patients with lymphoma, breast, head and neck cancers is now underway, with lab work being carried out into skin, liver and ovarian cancers.

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