There are two types of vaccines: preventative and therapeutic. Most vaccines we receive during childhood are for prevention, they stimulate the immune system to make antibodies and killer cells that remember the germ’s protein ID coating. Cancer vaccines are therapeutic, designed to be given after the person becomes sick with the disease. They often don’t work well because prevention is easier than treatment, and your immune system reacts differently towards “self” than to foreign bacteria and viruses, “non-self”.
Cancer cells come from your own cells that have lost their ability to control their growth. The immune system often doesn’t see the tumor cells as dangerous, just self cells. After all, when the immune system starts attacking the body, we call it autoimmunity. So, in a sense, cancer vaccines try to teach the immune system that something it sees as harmless is really a threat.
Some cancer vaccines try to stimulate antibodies, but these are small proteins that are usually inadequate to kill a tumor cell. Most vaccines try to stimulate killer cells to attack and destroy tumor cells the same way they would kill a cell infected by a virus. This can be done in several ways: by injecting the patient with their own cancer cells, killed by radiation and mixed with immune-stimulating chemicals, by injection with protein pieces of the tumor cell (peptides), and with Dendritic Cells (DC). DC vaccines are superior in many ways in that the can stimulate killer cells directly, instead of relying on other cells to help out.
Sunday, March 29, 2009
Saturday, March 28, 2009
Melanoma Vaccines I
Because of the toxicity of chemotherapy and radiation, doctors have tried to harness the power of the immune system to fight cancer. The immune system has many specialized units, but it is the killer cells, or Cytotoxic T Lymphocytes (CTL), that are most important in cancer immunotherapy. These white blood cells “feel” other cells to find a protein called the HLA complex on the cell surface. This serves as an ID, so transplanted organs are matched to similar HLA types. The HLA complex also carries samples of the proteins made in the cell. This is important because viruses hijack cells and force them to make viral parts, which are packaged into HLA and shown to the killer cell Health Inspector, which destroys the cell.
The killer cells get their information from cells called Dendritics, (DC), which act as scouts for the immune system. They take up bits of germs and show them to the killer cells for targeting purposes. The DC can be cultured from whole blood, so DC vaccines allow us to program the immune system like a computer. This has tremendous potential for the field of cancer vaccines.
The killer cells get their information from cells called Dendritics, (DC), which act as scouts for the immune system. They take up bits of germs and show them to the killer cells for targeting purposes. The DC can be cultured from whole blood, so DC vaccines allow us to program the immune system like a computer. This has tremendous potential for the field of cancer vaccines.
“One Size Fits All” Cancer Drugs
For a drug candidate to receive serious consideration for drug company funding, it has to fit a certain business model. Currently, the preferred model is a pill or liquid that can be injected into the patient. These drugs tend to have a single pathway of action against the cancer cell. Mutations in the tumor cell can quickly render the drug useless. If this is the case, why do companies continue down this road to failure? Basically, these business models are the only ones they know. These types of drugs fit into an established system of production, shipping, storage, administration, and billing. This model works well for simple diseases, but cancer is unique in that no two patients with the same type of cancer are alike. We can even demonstrate that in a melanoma patient, the tumors on their legs are genetically different than the ones on their back. It’s like having 100 different kinds of crabgrass weed growing on your lawn. By the time you have tried five different weed killers, you lawn is dead from the accumulated toxins.
The Business Model of Cancer Drugs
Fiction writers and Hollywood love to paint a story of the cure for cancer being locked up in a vault in Switzerland by evil corporate henchmen. First, a cure would be patentable, and so it would be worth billions to whoever owned the patent. The idea that a for-profit firm would refuse to sell a profitable product is pure fiction. Cancer kills one out of five people, including Pharmaceutical CEOs and FDA Scientists. If there was a proven cure out there, we would all know about it.
Instead of a conspiracy to prevent a cure, what we have are a set of systems that work to prevent promising treatments from being tested. This is not intentional, but is the result of financial and regulatory decisions by business and government agencies. Take the FDA, for example. This agency is mostly staffed by smart, hard-working people making a lot less than their industry counterparts. They would love to see improved treatments, after all, their kids and their neighbor’s kids get leukemia, too.
Unfortunately, if you have a brand-new therapy for cancer, FDA makes you try it on the sickest patients, who have already failed previous, approved treatments. We know from animal tests that if we could intervene earlier in the disease process, we would get better outcomes. Testing a new treatment on the sickest patients is like pouring a new brand of racing fuel in a 1975 Chevy Vega and expecting it to win the Indy 500.
Another myth is the Company Research Department. While there are many excellent researchers in private firms, these are businesses with an obligation to make money for their shareholders. There is nothing wrong with this setup, but there are two main problems at work here, First, there are lots of dead ends in drug discovery, to the smart companies have learned to feed higher off the food chain. This involves letting academics do the bulk of the tedious screening process, (with Federal Grant Money), then, they can cherry-pick the most promising treatments, fund the remaining research steps, and patent the drug. Another way is to take an already-approved drug and modify it to either extend the patent or make a new patent on it entirely. There is a joke around the Bay Area about a BioTech giant that they “hire more lawyers than doctors”.
So, now you have a new therapy with real potential, but it doesn’t fit the business model gold standard of a pill or liquid. Remember that single-action pills work well for simple diseases by fixing one machine in the factory, but we’re trying to fix the whole factory. So, if your new drug is a pill, it fits the companies’ business model (hooray!), but its simple action means that it’s usually a matter of time before the cancer cells mutate and are no longer vulnerable to the drug. It’s like hitting mosquitoes with DDT, the first time, you kill 99.99%, but the few resistant ones multiply, and pass on their genes, and now the whole population is resistant. This is why cancer drugs often work well for a few months, than lose their effectiveness.
You probably think an effective drug is one that will cure a majority of patients who take it. However, to a drug company, an effective cancer drug is one that works well enough to get FDA approval, and can be sold for a high profit margin. That’s why you see drugs that cost $10,000/month which add a few months of average survival to the patients who take them. There is nothing evil in this system, it’s just business. Pharmaceutical companies know how difficult it is to cure cancer, so they figure a poor, but profitable, solution is better than no solution at all.
Instead of a conspiracy to prevent a cure, what we have are a set of systems that work to prevent promising treatments from being tested. This is not intentional, but is the result of financial and regulatory decisions by business and government agencies. Take the FDA, for example. This agency is mostly staffed by smart, hard-working people making a lot less than their industry counterparts. They would love to see improved treatments, after all, their kids and their neighbor’s kids get leukemia, too.
Unfortunately, if you have a brand-new therapy for cancer, FDA makes you try it on the sickest patients, who have already failed previous, approved treatments. We know from animal tests that if we could intervene earlier in the disease process, we would get better outcomes. Testing a new treatment on the sickest patients is like pouring a new brand of racing fuel in a 1975 Chevy Vega and expecting it to win the Indy 500.
Another myth is the Company Research Department. While there are many excellent researchers in private firms, these are businesses with an obligation to make money for their shareholders. There is nothing wrong with this setup, but there are two main problems at work here, First, there are lots of dead ends in drug discovery, to the smart companies have learned to feed higher off the food chain. This involves letting academics do the bulk of the tedious screening process, (with Federal Grant Money), then, they can cherry-pick the most promising treatments, fund the remaining research steps, and patent the drug. Another way is to take an already-approved drug and modify it to either extend the patent or make a new patent on it entirely. There is a joke around the Bay Area about a BioTech giant that they “hire more lawyers than doctors”.
So, now you have a new therapy with real potential, but it doesn’t fit the business model gold standard of a pill or liquid. Remember that single-action pills work well for simple diseases by fixing one machine in the factory, but we’re trying to fix the whole factory. So, if your new drug is a pill, it fits the companies’ business model (hooray!), but its simple action means that it’s usually a matter of time before the cancer cells mutate and are no longer vulnerable to the drug. It’s like hitting mosquitoes with DDT, the first time, you kill 99.99%, but the few resistant ones multiply, and pass on their genes, and now the whole population is resistant. This is why cancer drugs often work well for a few months, than lose their effectiveness.
You probably think an effective drug is one that will cure a majority of patients who take it. However, to a drug company, an effective cancer drug is one that works well enough to get FDA approval, and can be sold for a high profit margin. That’s why you see drugs that cost $10,000/month which add a few months of average survival to the patients who take them. There is nothing evil in this system, it’s just business. Pharmaceutical companies know how difficult it is to cure cancer, so they figure a poor, but profitable, solution is better than no solution at all.
The Cancer Cell as A Factory
It seems like every month, the media reports another cancer breakthrough discovery. Excitement and hope flare for a few weeks, but then the new drug fades into the background. What’s going on in those labs? We have to remember that cancer is a much more complex process than diabetes, high blood pressure, and heart disease. These conditions are caused by one cell process controlled by a hard-working protein called an enzyme. It’s like a car factory where 99% of the different assembly lines are doing fine, but one machine controlled by one operator is turning out a bad part. The drug either blocks the bad part of the machine or helps the good part compensate, and the part comes out OK.
Now picture a cancer cell, where instead of one bad machine, there is chaos as each line turns out different parts: helicopter, submarine, lipstick case, etc. The whole factory is in need of repair. That’s what the researchers are trying to fix, and it’s the difference between changing a flat tire by the side of the road and changing the gears on the transmission while driving 70 mph on the freeway. No wonder there are so many crashes on the road to discovery.
Now picture a cancer cell, where instead of one bad machine, there is chaos as each line turns out different parts: helicopter, submarine, lipstick case, etc. The whole factory is in need of repair. That’s what the researchers are trying to fix, and it’s the difference between changing a flat tire by the side of the road and changing the gears on the transmission while driving 70 mph on the freeway. No wonder there are so many crashes on the road to discovery.
Saturday, March 21, 2009
How Cancer Treatments are Supposed to Work
Cancer treatments fall into five major categories: surgical removal, chemotherapy, radiation, immnuotherapy, and small molecules. The first, surgery, is the oldest and most straightforward. Find the tumor and cut it out. This can cure the patient if the disease has not spread to other areas of the body. Chemotherapy, or cytotoxic (cell-killing) agents are still the foundation of most cancer treatment regimens. These chemicals come in many forms, but they have similar ways of working in the body. A common misconception is that chemo kills cells directly. Rather, the agent damages the DNA of a cell, and when the cell attempts to divide, this triggers a self-destruct program. Radiation also damages DNA preventing cancer cells from dividing. The main problem with chemo and radiation is that they are toxic to all cells, both tumor and normal cells are affected. Cells with rapid turnover rates like hair, intestinal lining, and white blood cells to fight infection are devastated by these therapies. This "scorched earth" defense often results in a patient who is malnourished, anemic, and prone to infection in addition to the cancer.
Help Cure Cancer
Melanoma is the fastest-growing cancer type, with 50,000 new cases in the U.S., and over 200,000 worldwide each year. If found early, before the tumor penetrates to the living skin layers, it is nearly 100% curable by surgery. However, once it spreads to the lymph and bloodstream, five-year survival rates drop to less than 10% for those with melanoma tumors in the lungs, liver, and brain. The disease often strikes younger patients in otherwise perfect health, especially those with an active, outdoor lifestyle with its increased exposure to UV rays from the sun.
To add more to the melanoma fear factor, there are no effective treatments for the disease beyond surgical removal. A massive study of thousands of patients in Europe concluded that the standby drug for Stage III melanoma that has spread to the lymph system had no survival benefit compared to observation. For Stage IV patients, the only drug to show any effective result is a substance called Interleukin-2. The IL-2 treatments are so toxic that the patients must be in the hospital the entire time, and has a 5% rate of heart attacks for an equivalent rate of complete responses to the treatment.
New treatments are despeately needed, and there is tremendous potential for vaccines, which have been in the developing stages for the past 20 years. Vaccines have seen limited success because of science, business model, and regulatory hurdles preventing the most promising treatments from being tested in clincal trials.
To add more to the melanoma fear factor, there are no effective treatments for the disease beyond surgical removal. A massive study of thousands of patients in Europe concluded that the standby drug for Stage III melanoma that has spread to the lymph system had no survival benefit compared to observation. For Stage IV patients, the only drug to show any effective result is a substance called Interleukin-2. The IL-2 treatments are so toxic that the patients must be in the hospital the entire time, and has a 5% rate of heart attacks for an equivalent rate of complete responses to the treatment.
New treatments are despeately needed, and there is tremendous potential for vaccines, which have been in the developing stages for the past 20 years. Vaccines have seen limited success because of science, business model, and regulatory hurdles preventing the most promising treatments from being tested in clincal trials.
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