New cancer drug ‘could be a blockbuster’

Cancer is the leading killer of New Zealanders, but there is an enormous effort going on here and overseas to find more effective treatments. Herald health reporter Martin Johnston today begins a two-day series looking at some of the drugs being developed at a world-renowned scientific discovery unit, the Auckland Cancer Society Research Centre.

New Zealand researchers have designed a new drug they believe could become a powerhouse, treating a wide variety of cancers by unleashing the body’s own immune system.

The University of Auckland’s UniServices company is negotiating with a potential biotech partner to run the first human trials of the new immunotherapy compound invented by scientists at the Auckland Cancer Society Research Centre and provisionally named SN38437.

“I think it has the potential to be a blockbuster,” said the head of the research project, Associate Professor Lai-Ming Ching.

It is expected to work against many of the difficult-to-cure solid tumours and blood cancers because they all use the same mechanism, targeted by the drug, to hide from the body’s cancer-killing immune system.

The development of the new drug will be featured at the research centre’s Conquering Cancer public open day on Saturday. This is part of the centre’s first annual research week, which is being held to mark its 60th anniversary.

The new drug homes in on the over-expression by cancer cells of an enzyme called IDO1 that they use to evade attack by the immune system. IDO1 breaks down an amino acid called tryptophan, causing a deficiency which cripples cancer-killing immune cells, allowing cancer cells to grow unchecked. The new drug is intended to block IDO1, unleashing the immune cells to recognise cancer cells as foreign and mark them for destruction.

“A lot of different cancer types, all the major ones, express [IDO1], practically everything that scientists have looked at,” said Dr Ching. A clear relationship had been found: the more IDO1 a tumour produces, the worse a patient’s survival chances are.

Cancer researchers’ interest in IDO1 was sparked by work in the late 1990s showing the enzyme is expressed by fetal mice, preventing the mother’s immune system from identifying them as foreign and killing them. But IDO1 is not turned on in most normal tissues, says industry publication Chemical & Engineering News. “The hope is that this limited activity will make it a safer drug target.”

IDO1 inhibitors are a form of immunotherapy, an approach which includes cancer vaccines. It also includes the new “checkpoint inhibitors” Keytruda and Opdivo that block the chemical signals that act as a tumour’s “invisibility cloak”, allowing the immune system to recognise and get on with killing the cancer.

Dr Ching’s group assessed more than 40,000 chemical compounds in their search for molecules to inhibit IDO1. The most promising compounds were modified to improve their properties as drugs before a “lead compound” was singled out to promote for human trials.

Two other IDO1 inhibitors are already in trials overseas.

“Ours does all the things the two in clinical trials can do and is better able to enter cancer cells,” said Dr Ching.

She hopes that clinical trials of SN38437 can be run in New Zealand. A drug’s first trials are to assess toxicity and find the right dose. A full series of trials to check safety and effectiveness could take five years.

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