Science Editor

The presentations at this year's annual meeting of the American Association for Cancer Research could, at first blush, leave one wondering whether anything at all is new in cancer research. Plenary talk topics included more stalwarts than unknowns, with cancer stem cells and apoptosis inhibitors both prominently featured, while a press conference on Sunday reported, among other things, the use of kinase inhibitor combinations and T cells - all approaches which, however useful they may turn out to be, simply cannot be characterized as new.

But some of the presenters argued that while the idea that cancer stem cells make a good target, and that drug combinations or T cells are good targeting agents may not be new, methodological advances have allowed recent progress in bringing those ideas to fruition.

In his plenary talk on "What makes cancer stem cells tick," John Dick, of the University of Toronto, gave a cogent description of the hopes attached to cancer stem cells - and the pitfalls such hopes can bring. With the discovery that solid tumors as well as hematological cancers seem to have stem cells, "there is now a flurry of papers that seem to be spotting cancer stem cells everywhere - in fact, there is almost breathless excitement that cancer stem cells are going to solve all the problems in cancer."

This despite the fact that the concept of cancer stem cells dates back to the 1960s.

Dick described a series of papers, based on cell labeling in leukemia patients, that led to its authors hypothesizing that there might be a subset of stem cells that are critical for renewing the cancer.

He recommended these papers, from the laboratory of Bayard Clarkson (who is still active at Memorial Sloan-Kettering Cancer Center) to everyone on the cancer stem cell field: "They remain as fresh today as they were when they were written, and remarkably prescient."

But at the time, the assays to separate and test different populations of cells were not available, making it impossible to test whether there is such a thing as a cancer stem cell. "One proves or disproves the [cancer stem cell] model based on prospective isolation," he said.

Modern techniques do allow the isolation of different cell populations, and have allowed Dick's laboratory to isolate a putative group of acute myelogenous leukemia stem cells, and find an antibody that may be effective against them. That antibody is now in clinical trials.

Beyond the news of yet another antibody in early stage trials, Dick stressed the continued importance of "Some of the [mouse] tumor models may not be as reflective as they need to be," he said.

In some mouse models, for example, the frequency of putative stem cells can exceed 10 percent, which makes it hard to argue that such cells are stem cells in any meaningful sense. For this reason, some scientists have sounded "a note of caution" amidst the high-flying hopes for cancer stem cells.

But, he added, such disagreements are precisely what moves knowledge forward. "What controversies do is they sharpen science and they weed out sloppy thinking. And we sorely need that," he said.

T cells, too, have been around the block a few times, as Boston University researcher Richard Junghans acknowledged at a press briefing titled "Bench to Bedside: What's on the Horizon" on Sunday.

At the briefing, Junghans presented data on a genetically modified T cell engineered to have a chimeric receptor - consisting of the binding domain of an antibody - that essentially, Junghans said, "fools the T cell into thinking the cancer has a virus infection."

The antibody is now in a Phase I trial. Junghans presented data from the first two patients, who had a 50 percent and 75 percent reduction, respectively, in their blood level of prostate-specific antigen over the two months following the T-cell infusion.

While Junghans called such reductions "unsatisfactory," he also noted that the patients are receiving the lowest dose in a dose-escalation study; once three patients have been treated at the current dose level, the next dose will be tenfold higher.

T cells, of course, have been nearer to the bench than to the bedside for a long time. A 1998 article in the New York Times was headlined "Laboratory reproduction of patients' immune cells holds substantial therapeutic potential." But Junghans was optimistic that real progress is at hand, predicting that "the FDA will have approved one of these designer T-cell constructs - if not this one, then some other one somewhere - as standard therapy within the next five years."

Junghans said that two recent advances are at the root of his optimism. For one, new procedures for engrafting the T cells, should lead to better engraftment and stronger activity.

Additionally, he said, the newest generation of designer T cells is "more complex" than its predecessors, often incorporating several signals that enable the T cell to respond to different pathways. A newer version of his T cells has an additional signal that can reactivate the T cell even if it goes into a resting state once it makes contact with an antigen.

"All these technologies take a while to mature," he said. But these technological advances "give me much more optimism about the next five years or so."