November 18, 2010
Gene Therapy Immune Tweak Kills Melanoma In Mice

Complete melanoma remission in mice was achieved with gene therapy to turn up the immune system against the cancer.

INDIANAPOLIS A potent anti-tumor gene introduced into mice with metastatic melanoma has resulted in permanent immune reconfiguration and produced a complete remission of their cancer, according to an article to be published in the December 2010 issue of the Journal of Clinical Investigation. The online version is now available.

The cloned gene came from a patient with melanoma and the gene amped up immune response to melanoma.

Indiana University School of Medicine researchers used a modified lentivirus to introduce a potent anti-melanoma T cell receptor gene into the hematopoietic stem cells of mice. Hematopoietic stem cells are the bone marrow cells that produce all blood and immune system cells.

The T cell gene, which recognizes a specific protein found on the surface of melanoma, was isolated and cloned from a patient with melanoma. The gene-modified stems cells were then transplanted back into hosts and found to eradicate metastatic melanoma for the lifetime of the mice.

A result like this will take years before it is tried on humans. But why? If you've been given a malignant melanoma diagnosis death sentence by a doctor why shouldn't you be allowed to get highly experimental gene therapies? That people with fatal diseases can't bypass the drug approval process and try anything that works on lab animals just seems immoral to me.

Share |      Randall Parker, 2010 November 18 10:32 PM  Biotech Cancer

Nick G said at November 22, 2010 11:39 AM:

That people with fatal diseases can't bypass the drug approval process and try anything that works on lab animals just seems immoral to me.

Only, only, only if the people providing the therapy are strictly prevented from charging for it. People will pay anything for hope, and a lack of controls would open the door to enormous levels of heartbreaking medical scamming.

Mike G said at November 22, 2010 12:04 PM:

The federal government isn't your Mom Nick.

Only children and the mentally deficient need protection from the unscrupulous.

spool32 said at November 22, 2010 12:33 PM:

The appearance of impropriety would make a mess of things, though. I agree, the FDA should open these experiments up for humans with a prognosis of early death on condition the researchers don't charge.

Of course... there's another wrinkle here: once you have the gene incorporated into your body... can you give anyone else your blood? Is it legal to stop you?

skin path person said at November 22, 2010 12:56 PM:

I'm a skin pathologist by trade, and literally as I type this message, I have on my desk a specimen of metastatic melanoma from a close family friend I'm reviewing. So I'm not unsympathetic here.

The quick answer is that what works in lab rats doesn't always work in human beings, and these sort of treatments aren't always risk free. Again, from experience, I've watched the autopsy of a 27 year old woman who was directly killed by side effects of an experimental cancer therapy in a controlled research setting. As another consideration animal melanomas behave differently than human ones.

The right thing to do is to do the basic research (which may, or may not involve animal models), work out an appropriate research protocol, then try it on human beings. That's the only real way you're ever going to be able to measure a particular therapy's real world efficacy.

In practice, a therapy such as this one requires a bit of genetic engineering, then a bone marrow transplant. This can't be done in someones garage. It requires quite a bit of technical and clinical knowledge, and it *MUST* be done at a specialized center.

Its also going to be ghastly expensive. Where is that money going to come from? Its not fair to expect insurance companies to pay for expensive and unproven therapies, the costs of which get transferred to their customers. The money has to come from either public research (ie tax money) private endowments, or from commercial enterprise. In any of those cases, the ones making that investment into the therapy SHOULD at least expect that it be done with the idea of creating a generally available therapy. Going outside the accepted research system to try and cure one person in a non-investigatory setting may help that person. . .it may not, but it won't really go towards helping to make a "cure" which might end up saving thousands or tens of thousands of lives.

All that said, in theory, I'd have no problem with anyone rich enough who wanted to pay for this themselves to be their own guinea pig. In practice, though, it would be next to impossible to find any reputable researcher willing to try this outside of a clinical research setting, since at best there would be tremendous ethical issues at play, at at worst serious medicolegal liability ones.

Doug Collins said at November 22, 2010 12:56 PM:

Would blood transmit the gene? It sounds like the lentivirus was used on marrow cells.

skin path person said at November 22, 2010 1:05 PM:


You presume that this thing is even ready for clinical trial in humans. It probably isn't, though when (if) it is, I'd guess there won't be any shortage of individuals with metastatic melanoma willing to sign up as human guinea pigs.

In response to your other comment, individuals with a history of metastatic malignancy are supposed to be excluded from the blood donation pool via questionnaire screening at the time of donation. So in practice, the issue of what happens when they donate blood is moot. . .they aren't allowed to donate blood.

In theory even if they did lie about this just to donate blood anyway (why would they?. . .don't know), I doubt the genetic manipulation here would hurt anyone receiving just packed red blood cells from the donors.

Unless they were immunosuppressed, their own functioning immune system would (should) kill off the small number of circulating peripheral stem cells that might have come along for the ride along with red blood cells. Immunosuppressed individuals are supposed to receive irradiated blood units specifically to prevent the establishment of stem cell engraftment.

Viator said at November 22, 2010 1:11 PM:

All well and good but AIDS patients quickly caught on that the FDA approval protocol was a deadly roadblock.

"As consumers-the constituency the FDA was supposed to protect-AIDS activists were particularly difficult for the agency to ignore. Well-organized, highly visible, and knowledgeable about the drug approval process, they made effective use of the media to communicate their concerns. Extensive congressional hearings explored charges of a lack of responsiveness on the part of the FDA and the appropriateness of its restrictions on access to drugs. The FDA responded to this pressure through several measures designed to expedite access to AIDS treatments: treatment use of investigational new drugs (IND), liberalized interpretation of import regulations, subpart E regulations to speed the approval process, and the parallel track proposal to allow drug access early in the testing process."

So they carved out special treatment for themselves. The rest of Americans still mill around like sheep.

"ACT UP successfully used its nonviolent, direct-action approach to force the FDA to accelerate drug trials for AIDS and to consider ACT UP's "parallel track" proposal. Under this proposal, people with AIDS are given drugs before they are approved by the time-consuming and bureaucracy-ridden FDA approval process."

DngrMse said at November 22, 2010 1:55 PM:

"If you've been given a malignant melanoma diagnosis death sentence by a doctor why shouldn't you be allowed to get highly experimental gene therapies?"

The FDA. Gah, that was easy. The federal government is about representing itself, not the people that stupidly empower it.

Stephen Gordon said at November 22, 2010 2:30 PM:

That people with fatal diseases can't bypass the drug approval process and try anything that works on lab animals just seems immoral to me.

Immoral to both the dying patient and to future cancer sufferers that might benefit from this research.

Ellen said at November 22, 2010 2:43 PM:

The FDA has been trying to stop executions throughout the US because there is a shortage of sodium thiopental from the approved supplier. Arizona is probably going to be in trouble for using thiopental from a (shudder) British supplier. This shows how thoroughly concerned the FDA is about getting the job done perfectly. They'd rather stop everything than let something proceed in an unapproved manner. Life and death mean nothing; the procedure is the important thing.

bill said at November 22, 2010 2:56 PM:

If you read the article ....they ARE running Human trials.

"...It has paved the way for a new clinical trial in humans funded by the V Foundation for Cancer Research. The pilot phase I trial will involve treatment of 12 patients and focus primarily on the safety and efficacy of the therapy, said Dr. Touloukian, who is the senior author on the JCI paper and the principal investigator for the clinical study. The clinical trial is expected to begin accruing patients by late 2011."

Flappy said at November 22, 2010 4:39 PM:

Agree with you wholeheartedly. Unfortunately, I think the only way to effect change is formal lobbying. Take Adam Walsh as a model; you'd need donors, volunteers, and something like a "Survivors PAC."

Randall Parker said at November 22, 2010 9:24 PM:


Yes, 12 patients starting at least a year from now. That's still slow. People are dying every day from this disease.

skin path person,

I get that most of the things that work on lab animals won't work on humans. But if I've ever got 6 months left to live my take is going to be to try anything. If it does not work and I die in 3 months rather than 6 months it is not like those last 3 months are a great loss. I'd rather take the gamble and at least help rule out a failed treatment more rapidly.

Part of finding successful treatments is iterating thru lots of possible treatments. A lot of people dying from cancer would be willing to try experimental treatments that have only worked in lab rats to date. I say let them.

Money: Well, plenty of rich people are dying from cancer. So there'll be no shortage of rich people willing to try. Also, if all one has left is 6 months and a $300k house then why not sell the house and take one last stab at curing the disease?

Nick G said at November 23, 2010 11:11 AM:

Money: Well, plenty of rich people are dying from cancer. So there'll be no shortage of rich people willing to try. Also, if all one has left is 6 months and a $300k house then why not sell the house and take one last stab at curing the disease?

You're working from the assumption that the people selling the treatment will be at least somewhat reputable. I think your perspective is shaped by the conservatism of the FDA.

There is an analog in criminal law. As long as civil protections for defendants are strongly enforced, it looks tempting to loosen them. OTOH, the year before the Supreme Court created the exclusionary rule, guess how many warrants were issued for searches in NYC: zero. none.

Now, there should be a range somewhere between the current glacial pace of research, and a 1890's style free-for-all. But, I think it would have to be developed very carefully. Just allowing anybody who wants to to be vulnerable to scamsters who are perfectly willing to have people sell their houses to buy snake oil is not ok.

Anonymous said at December 31, 2010 11:46 AM:

If it's OK to let a perfectly healthy/sane person strap themselves into an experimental aircraft and risk a 1 in 20 (or lower) chance of dying I see no problem in letting a dying/sane person take a potentially life saving risk. Just saying.

Stage 1 MM survivor.

Mike said at May 18, 2011 10:12 AM:

Here is a site for skin path person to evaluate wrt the family friend with melanoma:

Here are some unrelated clinical trials at NIH.

I have other information that may also be helpful. Hope this info is not too late.


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