A new wave of experimental cancer drugs that directly recruit the immune system's powerful T cells are proving to be immensely effective weapons against tumours, potentially transforming the $100bn global market for drugs that fight the disease.
But, reports Reuters Health, top oncology researchers are concerned about the two emerging technologies, citing dangers seen repeatedly in clinical trials including the potentially fatal build-up of toxic debris from killed tumour cells and damage to healthy tissue. Such side effects could block regulatory approval if they aren’t controlled, researchers and drug company executives said.
In some trials, the two new approaches, known as CAR T cells and bispecific antibodies, have eliminated all traces of blood cancers in 40% to 90% of patients who had no remaining options. CAR T cells, or chimeric antigen receptor T cells, are T cells that have been removed from the body and attached through genetic engineering to an antibody fragment that recognises a specific tumour protein. T cells are an especially powerful disease-fighting kind of white blood cell. The result is a drug with the killing power of a greatly enhanced T cell, combined with the tumour-spotting ability of an antibody.
Bispecific antibodies are a twist on conventional antibodies, Y-shaped proteins whose two arms grasp for the same protein target found on cancer cells. With bispecifics, one arm of the antibody typically grasps a cancer cell while the other arm takes hold of T cells, bringing the mortal enemies into contact. The T cell punches holes into the adjacent tumour cell and injects deadly enzymes. Conventional antibodies, by contrast, don't directly recruit T cells.
The potency of the experimental drugs comes with some dangerous potential side effects, however. In the killing process, inflammatory chemicals from the medicines and the tumour cells, called cytokines, are released into the bloodstream and can cause fever, low blood pressure and rapid heartbeat that can be life-threatening.
The drugs, because of their unique structure and how they work, make it harder to predict whether they will go astray, said Dr Bindu George, team leader of the US Food and Drug Administration's Office of Cellular, Tissue and Gene Therapies.
Most CAR T cells and bispecific antibodies in development identify blood cancer cells by a specific protein, CD19, found on the surfaces of lymphomas and leukaemias. Because the same protein can also be found on non-cancerous cells, the drugs can go off track and attack healthy tissues. "Our biggest concern would be an off-target toxicity that wasn't expected and we didn't know the cause of it," George said. In that case, "we might have to ask (the drugmaker) for additional information, how the toxicity happened, what organ it was, and literally go back to the drawing board."
[link url="http://www.reuters.com/article/2015/01/26/us-cancer-advances-idUSKBN0KZ0BZ20150126"]Full Reuters Health report[/link]