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Hi,

I just read this in my local newspaper. Thought it sounded interesting.

Killer T-cells wipe out leukaemia

From correspondents in Washington
From: AFP
August 11, 20117:23AM

THREE US cancer patients were brought back from the brink by a new therapy that turned their own immune cells into tumour killers, wiping out an advanced form of leukaemia, researchers said today.

The breakthrough stunned scientists and although the gene transfer therapy technique is still in development, it could offer hope one day to people who suffer from ovarian, lung, breast and skin cancers.

"We saw amazing results," said Michael Kalos, lead author of the study that appeared in Science Translational Medicine and was published simultaneously in the New England Journal of Medicine.

"These were nasty tumours that were late-stage, a lot of mutations that had bad prognosis," he said. "We saw massive reduction in tumour burden. One patient had over seven pounds (three kilograms) of tumour and it all disappeared."

Two of the three men in the study with chronic lymphocytic leukemia (CLL) have remained cancer-free for almost a year, while the third has seen a slight recurrence of disease.

"Within three weeks, the tumours had been blown away, in a way that was much more violent than we ever expected," said senior author Carl June, who like Kalos is a researcher at the University of Pennsylvania.
"It worked much better than we thought it would."

Scientists removed a sample of the patients' T-cells and genetically modified them to attack all cells that express a certain kind of protein, CD19, which includes tumour cells.

They altered them using a lentivirus vector that encodes an antibody-like protein known as a chimeric antigen receptor. The protein is expressed on the surface of T-cells and designed to bind to CD19.

The scientists also engineered the T-cells to start triggering other T-cells to multiply as soon as they attached to a cancer cell, bringing on a faster death for the tumour but avoiding the side-effects of cancer drugs.

"We saw at least a 1000-fold increase in the number of modified T-cells in each of the patients. Drugs don't do that," said Mr June, describing the infused T-cells as "serial killers".

"On average, each infused T-cell led to the killing of thousands of tumour cells."

In one case, a 64-year-old man had blood and marrow "replete with tumour cells".

He saw little change for the first two weeks after treatment, but then started experiencing nausea, chills and fever.

Tests showed he was undergoing a huge rise in T-cell count, and a condition known as tumour lysis syndrome that can arise when cancer cells are dying off.

By day 28, his blood showed no evidence of leukaemia.

A 65-year-old patient saw similar results, with no trace of leukaemia after a year, but a 77-year-old patient saw a slight recurrence of cancer after he was treated with steroids for the symptoms of tumour lysis syndrome.

However, his tumour load remains far below what it was before the treatment.

Steven Rosenberg, chief of the surgery branch at the National Cancer Institute, described it as "important" and "impressive". He was not involved with the study but has published research on similar approaches to eradicating B-cell lymphomas and melanoma.

"You are taking advantage of the body's immune system by creating outside the body T-cells that can act against the cancer," he said.

"You have to select the particular gene modification for each type of cancer but when you pick it wisely it can be very effective."

The other main form of treatment, bone marrow transplants, carries a minimum 20 per cent risk of dying from the procedure and cure rates hover at around 50 per cent.

While it remains unknown how long the treatment may keep cancer at bay, researchers were excited to see that "memory" T-cells remained months after the cancer disappeared, indicating the body is retaining some protection.

The next step is to try the technique in two children and at least 13 adults with CD19-positive leukaemia.

They are also looking to determine whether the approach could target non-Hodgkin's lymphoma and acute lymphocytic leukaemia, mesothelioma cancer cells, ovarian and pancreatic cancer cells.

Chronic lymphocytic leukaemia is the second most common type of adult leukemia after acute myeloid leukemia, according to the National Cancer Institute.

"I'm healthy and still in remission," said one of the three patients, who declined to be named. "I know this may not be a permanent condition, but I decided to declare victory."