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Como funciona a imunoterapia do câncer

Excelente artigo, da Economist, explicando a imunoterapia do câncer:

Doctors are trying—with some success—to recruit the immune system to help with the war on cancer

Since there are now treatments aimed at more than one checkpoint protein, one question was whether a combination might be more effective than any one drug alone. 20150606_STC514Research presented to the conference suggests that it is. Progression-free survival in melanoma (in other words, the amount of time during which a patient’s cancer did not become worse) was 6.9 months for those on Opdivo alone and 2.9 months for those taking only Yervoy. Patients given both, though, posted an average time of 11.5 months (see chart).

Checkpoint inhibitors seem to work with other types of cancer, too. Keytruda is effective against some colon cancers and in metastatic head-and-neck cancers. Opdivo, now approved to treat a common form of lung cancer, has shown early promise against liver cancer. Propitious results have also been seen in bladder and kidney cancers. For late-stage lung cancer, where the best treatment is chemotherapy, the fraction of people still alive after five years is typically just 5%. Combinations of immuno-oncology drugs have boosted this to between 20% and 30%. A blizzard of treatment-comparison studies is under way.

Miracles are rare in medicine, and doubly so in oncology. Those encouraging—even spectacular—lung-cancer numbers hide big disparities. Although some patients get a long-term reprieve, there are more for whom checkpoint inhibitors make little difference, or even none at all.

One theory is that some tumours may be employing Dr Bradley’s first avenue of escape; instead of (or as well as) trying to hide from a T-cell response, they try to avoid provoking such a response in the first place. Juno Therapeutics, in Seattle, hopes its CAR-T therapy will close that route off, too. This involves extracting T-cells from a cancer patient and modifying them with gene therapy so that they produce a tumour-recognising protein on their surfaces. These cells are multiplied in a dish and put back into the patient’s body.

Immune Design, another Seattle firm, wants to do something similar, but from within. It has created a virus that can alter the genetic make-up of dendritic cells, the immunological sergeant-majors responsible for educating T-cells about new threats. Alongside the virus are an antigen and an adjuvant, harmless substances that stimulate T-cell production. The hope is the cocktail will produce an army of primed T-cells.

Checkpoint, counterpoint

Some, maybe many, of the patients who do not respond to checkpoint blockers at the moment might do better if they were given a simultaneous dose of T-cells that already recognised the enemy. It might also be prudent to revisit cancer vaccines to see if their effectiveness improves when used in combination with checkpoint inhibitors. Perhaps they were doing a good job in setting up an immune response only to have the tumours promptly dampen it.

If combining the different forms of immunotherapy with each other offers promise, so does combining them with the mainstays of cancer treatment—an area in which there is now a lot of research. They might be useful just after surgery, for instance, to mop up any stray cells that the surgeon’s knife has missed. They may work well, too, with the targeted therapies that try to choke off tumour growth at the source. Tumours often develop resistance to such targeted therapies; hitting them with a biological double-whammy might make that less common.

The new treatments look promising. But they do not look cheap. Yervoy costs $130,000 per patient per year, Opdivo about $150,000. As more drug companies pile in, patients can hope that competing drugs will hit the market soon. But as the rich world grows older, fatter and therefore more cancer-prone, one salient question is how lucrative immuno-oncology might prove for drugs firms—and how affordable for the insurers and governments that would have to buy them.

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