Altered Immune Cells Help Girl Beat Leukemia

An anonymous reader writes "For decades, one of cancer's most powerful weapons has been to corrupt the human immune system. Finally, researchers in Philadelphia have developed a way to turn that weapon against certain cancers, and potentially open the door to a whole new generation of therapies for all manner of cancers. From the article: 'It is hard to believe, but last spring Emma, then 6, was near death from leukemia. She had relapsed twice after chemotherapy, and doctors had run out of options. Desperate to save her, her parents sought an experimental treatment at the Children’s Hospital of Philadelphia, one that had never before been tried in a child, or in anyone with the type of leukemia Emma had. The experiment, in April, used a disabled form of the virus that causes AIDS to reprogram Emma’s immune system genetically to kill cancer cells.'"

Comments

Are you sure you're a doctor?

[kc9jud]

http://xkcd.com/938/

Re:Are you sure you're a doctor?

[Guppy]

I am not a doctor, but I am a med student. :)

Historically, our techniques for treating cancer can be categorized into three categories: chemotherapeutics/radiation which attack rapidly dividing cells indiscriminately; "magic bullet" chemotherapeutics which exploit specific quirks of a cancer's biology -- a feature that differentiates it from normal cells (the perfect solution, but far too few such exploits are known); and immuno-therapeutics that utilize the body's own defenses. In practice, many techniques combine some aspects from the different approaches.

The immuno-therapeutic approach has a long history, beginning with Coley's Toxins, and there are a few cases where a cancer is naturally immunogenic enough for it to work (for instance, using BCG to evoke a response to certain kinds of bladder cancer). It has been hypothesized that the immune system eliminates most abnormal cells before they become cancerous, but the flip-side of this hypothesis, is that abnormal lineages which do become cancers, would only be able to do so because they gained mutations allowing them to evade or suppress that normal defense. In addition, while certain types of cancer increase in frequency in populations with long-term immune suppression (due to AIDS, organ transplant drugs, or some other acquired or congenital condition), many other types of cancer do not -- suggesting that in those cancer types, the immune system's normal tendency to avoid attacking the self, may alone be sufficient to shield them.

Anyway, what is particularly impressive about this CAR-T (Chimeric Antigen Receptors T-Cell) technique, that has been generating a lot of excitement, is its ability to completely and permanently break immune tolerance -- to the point where it does not need to target some identifiable abnormal feature of the cancer, but can target a completely normal feature of that cancer cell's lineage. In this case, the normal CD-19 receptor is targeted, and results in the entire population of B-Cells being wiped out. The leukemia is a sub-set of this cell population, so it is eliminated as well, with the bonus of a persistent immune response that continually suppresses any survivors. The downside is that the patient is left with no B-Cells to produce antibodies, and thus relies on periodic infusions of IVIG (Intravenous Immunoglobulin, consisting of antibodies pooled from donors) to protect against infection.

Re:Are you sure you're a doctor?

[Guppy]

What's the end game for this type of treatment

It's hard to say, but there's much potential here. Next antigen targets on their list include MAGE-A3 (melanomas, and some lung and other cancers), NY-ESO-1 (some testicular and other cancers), and Mesothelin (mesothelioma, and some ovarian and pancreatic cancers).

It may also be possible to apply this technique to some diseases other than cancer -- AIDS is on the list as well. While HIV normally generates a robust (but ultimately futile) immune response, it may be possible to enhance that normal defense, by using this technique to direct it into a more cell-mediated (as opposed to humoral) response, and also engineering the modfied T-cells to be resistant to HIV infection.

Re:Balancing potential deaths with real-today ones

[Anonymous Coward]

using lethal viruses to help us combat lethal cancers.

Big deal. Lots of things useful things are lethal. Hell, I was injected with a disabled lethal virus a couple weeks ago. Just in time to keep me from being part of this year's flu season. Pretty much every cancer treatment kills things. That's how they work. The goal is to kill the cancer without killing too much of the person with it.

Re:Balancing potential deaths with real-today ones

[omnichad]

That's how I always describe chemotherapy to the layman. It's taking just enough poison and hoping that the cancer dies first.

Re:Balancing potential deaths with real-today ones

[kwyjibo87]

"[using] a disabled form of the virus that causes AIDS"

While true, this is a poor way to describe a lentiviral vector, meant to invoke the idea of using HIV to kill cancer in the minds of readers not familiar with modern molecular biology. HIV is a type of virus called a lentivirus, which itself is a type of retrovirus, which means that it takes the RNA genetic code it has packaged in the virion, chemically transforms it into DNA, and integrates this DNA into the DNA of the infected cell. Lentiviral vectors are designed such that they do this part of the viral life cycle, but are engineered to lack the genes necessary to make more viruses, so the integrated virus is dead on arrival.

In this case, the researchers kept the normal HIV surface receptors so the virus would efficiently target and "infect" T-cells from the patient; normally, lentiviruses are given a generic non-HIV receptor so they can infect any cell type you might be using in your lab experiments. The lentivirus genome contained not the normal viral genes, but a chimeric T-cell receptor designed to stimulate an immune response against CD-19, a surface protein specific to B-cells. Once this chimeric gene is integrated, the T-cells will express it on their cell surface, and stimulate the immune system to target and destroy cells that have CD-19 on them; this kills all the B-cells in the body, both healthy and cancerous. This last point is a problem brought up by TFA, that the patient now essentially has a limited auto-immune disorder as the altered T-cells persist in her body and continue to point them immune system to targeting B-cells, leaving her partially immuno-compromised (which is the funny part about using the "virus that causes AIDS" to do this).

Knee Jerk

[headhot]

Wow there are a lot of people freaking out they are using HIV for this.

Um, relax, they didn't give the girl HIV, they re-engineered the virus into something new. The virus doesn't replicate in the to host. T-cells removed from the host are exposed to the engineered HIV. The engineered HIV then changes the DNA in the T-cells to allow it to attack cancerous B-cells. The T-cells are then re-injected and do their work. The T-cells continue to replicate, but the engineered HIV is not actually introduced into the body.

Re:Knee Jerk

[Kyusaku Natsume]

I would mod you up to 11. The drawback, aside the initial cytokine storm is the complete loss of B-cells. I suppose that they could store unaltered T-cells and return the unaltered T-cells after they confirmed cancer remission, in a tick-tock strategy to let the patient recover their healthy B-cells. HIV is only a vehicle, in the same vein a pill is a vehicle for medicine, nothing else.

Re:Knee Jerk

[Turminder Xuss]

Exactly and thankyou. It's like amputating the B-cells. Not a risk free procedure, the cytokine storm can kill and then the resultant immune deficiency effects must be managed. But a susceptibility to colds is a lot better than leukemia. The treatment targets all B-cells, whether cancerous or not. We are still not identifying and destroying cancerous cells only. That is when words like "cure" might get to be used.

Re:Balancing potential deaths with real-today ones

[Anonymous Coward]

Wikipedia's Cancer Immunology article discusses this, going as far as how exactly the immune system goes about dealing with development of cancer cells in the body. It's actually a very interesting read, as Wikipedia puts it in relatively simple terms, if you're not familiar with it at all.

I am not sure if the goal of this altered immune cells therapy is to activate this process further or equip the immune system to deal with cancer in a whole new way, though. I would imagine it strengthens this existing response, but I'm no expert on it.

Re:Balancing potential deaths with real-today ones

[Samantha Wright]

That's more than a little misleading. The drugs used in chemotherapy are chosen because they preferentially kill fast-growing tissue first, such as hair, the intestinal endothelium (lining), and tumour cells. It's not as simple as taking some arbitrary, nondescript "poison" under the assumption that the cancerous tissue is poorly equipped to handle all toxins; specific mechanisms are chosen to limit the impact that the drugs have on the rest of the body.

The GP also made a bad comparison since, as the AC also said, inactivated viruses in this form have no replicative ability whatsoever. They're just gene syringes. These same misconceptions arose the last time we discussed retroviral leukaemia treatments.