Zheng Cui's WBC Injections are Underway; No Results Yet

[Guest guest]

[This is a story from two years ago, but it fleshes out some of the

details of Dr. Cui's attempts to use injections from healthy people to

fight cancer in humans.

One downside is that the current clinical trial excludes those with a

hematologic cancer such as CLL, and forbids prior use of fludarabine,

a drug commonly used in CLL patients.

I've not seen any news of the on-going trial using injections of

neutophils (neutrophil granulocytes) system cells. As far as I know,

the work is on-going, but no results are available yet.

Again, not for CLL; not yet at least. I've contacted the researchers

as to why no blood cancers in the trial, but have not received an

answer. I assume it is because of the damaged immune system in blood

cancers.]

Cancer-Curing Blood

It's a discovery in animals that would change everything if it turns

out to be true in people. An injection of blood cells from

cancer-resistant mice cures cancer in ordinary mice.

The End of Cancer?

A universal treatment that would work against any type of cancer has

always seemed like a far-fetched fantasy. But now researchers at Wake

Forest University have made a discovery in mice that might one day

lead to a " magic bullet " against human cancers if it proves to be true

in people. Several years ago, the researchers identified a rare strain

of mouse immune to high, usually lethal doses of cancer cells. Now

they have shown that not only are these mice cancer-resistant, but

their immune cells are also capable of curing normal, non-resistant

mice of any type of advanced cancer.

As reported in Proceedings of the National Academy of Sciences, lead

researcher Zheng Cui and his team injected white blood cells from the

cancer-resistant mice into normal mice with aggressive cancers that

should have killed them in two to three weeks. Instead, their cancer

disappeared.

" Cancer cells had already developed a large tumor in the mice, and at

a different place [than] where we put the immune cells in, " says Cui,

" That would require the immune cells to find them at a different part

of the body and then track them down to the site and destroy the

cancer cells. "

The researchers have bred a large colony of the cancer-resistant mice,

all from one mouse they discovered in 1999.

In previous studies the team showed that the resistant mice can

survive very large doses †" up to 3 billion cells †" of any kind of

cancer. This resistance is passed on genetically in a " perfect

Mendelian single dominant gene pattern, " says Cui, since the trait is

transmitted to roughly half of each resistant-mouse's offspring. On

this basis the scientists believe the resistance mutation must be in a

single gene.

But after seven years of searching for the gene, the researchers have

yet to identify it. " There isn't any reason to think it's not a single

gene, it just turns out that analysis of that genetics is somewhat

more complex than one would have predicted, " says pathologist Mark

Willingham, a co-author of the paper.

Their past work also clearly showed that the gene worked by somehow

activating the immune systems of these resistant mice to selectively

target cancer cells. Their most recent research confirms that the

immune cells that do the cancer killing belong to the innate immune

system. They recognize cancer cells as foreign and attack them without

having any prior exposure to them.

" I think the surprise from this mouse model is that it involves a part

of the immune system that would not have been predicted, " says Willingham.

When the researchers isolated different types of innate immune system

cells from the resistant mice and tested them against cancer cells,

they got another surprise: the cancer resistance was not confined to

just one type of immune cell. " All [the types] can be independently

killing [cancer] cells without the other subtypes present, " says Cui.

A funder of the study, the Cancer Research Institute, which backs

immunological approaches to cancer diagnosis and treatment, is funding

collaborations with Bruce Beutler, M.D., an immunogeneticist at the

Scripps Research Institute, to help search for the gene, and with

D. Schreiber, Ph.D., a molecular immunopathologist at the

Washington University School of Medicine in St. Louis, who will test

the cancer-resistant cells on his mouse models of naturally arising

cancers.

Unconventional ideas

The researchers also developed a blood test that can identify the

cancer-resistant mice without having to challenge them with cancer.

They hope a similar test might help find and study cancer-resistance

in people.

" If this were to be the same in humans we could simply identify

cancer-resistant humans and to do the blood transfusion or white blood

cell transfusion without even knowing the mechanism to find out

whether it will work or not, " says Cui, " So that's obviously on

everybody's mind. "

The researchers say they've heard from many cancer patients and their

loved ones excited about the tantalizing possibility that blood and

bone marrow banks might also contain cancer curing cells. Cui points

out that it could take years to find the gene, and many more to

develop and test drugs that target it. In the meantime, his team has

begun to test blood samples from healthy people, and have found a wide

range of cancer-killing activity in humans. " We are forced and

compelled to do this kind of experiment ... I think it's our

responsibility as cancer researchers, " Cui says. But he also

acknowledges that he is having a hard time getting funding for this

approach. " It's obviously a very unconventional way of doing science

nowadays, " he says. " It's not mechanism-based ... it’s simple mimicry

of what happened in the mice. "

Indeed, cell biologist Jill O'Donnell-Tormey, executive director of

the Cancer Research Institute, says it's important to first understand

the genetic and biological basis of these cancer killing blood cells.

" There is some indication that a similar mechanism that we're seeing

in these remarkable mice are also present in humans but we think we

have a ways to go in terms of doing a good deal of research before we

can actually answer that question, " she says.

Cui says he would like to pursue both the conventional and

unconventional approaches. " We think there might actually be a

possibility we could do it without knowing the mechanism, " he says,

" but of course by knowing the mechanism you could devise many other

options, so if one thing doesn't work then you can also find different

ways using the same concept. So we think both directions are important. "

He notes, however, that if the cell-donation approach were to work in

people, it would not need to go through a long FDA approval process.

" All the delivery mechanisms are already in place and all the ethical

regulations for that direction are already in place. So if we can

identify cancer-resistant humans then they could start treating them

tomorrow if someone wants to pay for it. "

This most recent finding by Cui and his team was published in the May

16, 2006 Proceedings of the National Academy of Sciences (PNAS). The

research is funded by the Cancer Research Institute (CRI), National

Cancer Institute (NCI), and the Charlotte Geyer Foundation.