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FRANKFURT, Jan 6 (Reuters) - A class of treatments known as
antibody-drug conjugates (ADC) combine cancer-tracking proteins
with powerful cell toxins. The therapies are getting a fresh
start as dozens of drugmakers test a record number of new
compounds in people.
Nearly 20 years after the first ADC, Pfizer's
Mylotarg, was approved, developers say they are now getting a
handle on the technology that was long seen as an elegant
concept, but one that presented many clinical challenges.
* How do ADCs work?
Antibodies such as Roche's top-selling Herceptin
have been a mainstay of modern medicine because these immune
proteins can be engineered to bind to cancer cells, where they
interfere with growth.
With ADCs, drugmakers go a step further and attach cytotoxic
molecules to antibodies to destroy the cancer cells outright.
Roche's Kadcyla combines Herceptin with the agent mertansine
(DM1).
The antibodies' role in that combination has been described
as that of a Trojan horse, carrying the cytotoxic agent inside
the tumour, where it can be deployed.
* What progress has been made in ADC research?
So-called "linker" molecules that connect the cell-killing
payload to the antibodies have been refined to release the
toxins only when the drug is absorbed by a cancer cell.
Some early ADCs fell apart in the bloodstream, leading to
failure or unacceptable damage to healthy tissues.
Newer ADCs, such as AstraZeneca's and Daiichi Sankyo's
Enhertu, have also been designed to kill adjacent
tumour cells even after the initially targeted cell has
disintegrated.
* How do ADCs stack up against other novel cancer therapy
approaches?
The so-called CAR-T cell approach, in which patients' own
immune system cells are removed from the body and re-engineered
to recognise and attack cancer, has been a much bigger focus of
pharmaceutical industry investment.
Hundreds of studies are underway from companies like
Novartis and Gilead Sciences. Both drugmakers
already have therapies on the market that are pegged as
potential billion dollar products in annual sales.
But CAR-T cells, for now, are targeted at blood cancers,
while ADCs have proven effective against solid tumours. Most
CAR-T cells also must be custom made for each patient, requiring
huge infrastructure investments, while ADCs can be centrally
produced and shipped globally.
ADCs also face competition from another treatment approach
called bispecific antibodies. Bispecifics are complex
therapeutic proteins that can latch onto the body's immune cells
and connect them with cancer cells.
The number of bispecifics in the pipelines of drugmakers,
including Roche, GlaxoSmithKline and
Bristol-Myers Squibb, is roughly on par with ADCs,
according to Beacon Targeted Therapies.
(Reporting by Ludwig Burger; Editing by Michele Gershberg and
Dan Grebler)
