Update from the Krag lab Spring, 2016
What is known:
- Each cell in a cancer, like all of our normal cells, is an extremely complex biological machine. This means that there are thousands and thousands of cell parts that all work together to make a single cancer cell be alive. Cancer cells have to conduct themselves to some extent like a normal cell or they could not live and grow. So most of the cell parts in a cancer are not too different from a normal cell.
- But there are some cell parts in a cancer that are different. They are different because the cancer cell genetic code for that cell part is mutated. This means there is an error in the genetic code for that cell part. Some cancer cells have only a few mutated cell parts and some have many, even hundreds. It is these mutated cell parts that the immune system can target.
- I think of a cell kind of like a car. Lots and lots of parts that make the whole thing go forward carrying people and groceries. Normal cars have normal car parts. A cancer car would have a few weird parts, like a square steering wheel instead of a round one. If I looked a row of parked cars it would not take long to figure out which one was the cancer car.
- Immunotherapy, which uses our own immune system to fight cancer, is kind of like asking the immune system to look for the cars with square steering wheels.
- Yes, our own body does make antibodies against a cancer
- Yes, antibodies can powerfully inhibit a cancer
- A major problem is that the immune response, even though it can detect square steering wheels, does not generate a large enough response to make the cancer disappear.
There are two steps. The first is to create a cancer vaccine and the second is to boost the immune response in a special way.
First step- make a special vaccine:
We read the genetic code of a cancer and learn which parts of the cancer are mutated. Then we will make a vaccine from these mutated cancer parts. Most vaccine trials rely on the vaccine to make the cancer disappear. Unfortunately most vaccines do not make the cancer disappear even though there is an immune response to the vaccine. We have a different approach. We are using the vaccine to educate the immune cells in the vaccine draining lymph node. Then we remove the lymph node that contains all of the anticancer immune cells. In the lab we use these immune cells to produce anticancer antibodies.
Second step- Remove the vaccine-draining lymph node and use the immune cells that have reacted to the vaccine:
Again, the big problem with current cancer vaccines is that even though there are immune cells that learn to target the mutated cell parts in the vaccine, the size of the immune response is not big enough to make the cancer disappear.
We approach this differently. We know how to find the exact lymph node that is responding to the vaccine. In this lymph node are all of the special immune cells that have learned how to target the mutated cancer parts. We will remove this lymph node under local anesthesia. I am a surgeon and this can be done with a small outpatient procedure through a one inch incision.
From the lymph node we recover the millions of immune cells that have responded to the vaccine. This means that we have the immune cells that have learned how to target the mutated parts of the cancer cells. This is a big deal. In the lab we will rapidly sort out the immune cells that seem to be most capable of targeting the cancer. Then we can go into production mode. We can make the antibodies in the lab to any level that we want. We are not restricted by the limited response in the body. This means that we can deliver back to the patient, anticancer antibodies at high dose.
There are also other immune cells that do not make antibodies but learn how to attack cancer cells. We can boost these cells to very high levels and give them back to the patient as well. We believe that boosting the immune cells in the lab will allow the special anticancer immune cells to have a chance at making the cancer disappear.
- We have learned how to identify the mutated cell parts of a cancer.
- We have learned how to make the vaccine.
- We know how to identify and remove the vaccine-draining lymph node.
- We are now working on the methods to rapidly sort out which of the millions of immune cells recovered from the lymph node best target the cancer. It is a very important step but we have recently overcome the major hurdles to accomplish this.
There are many pieces to this new strategy. The immune system is smart but it just does not expand the anticancer activity far enough. We intend to use our approach to greatly boost the immune response. Right now we are working in collaboration with multiple labs to establish the best method to identify the immune cells from the lymph node that have the best response to the cancer. This means dealing with single immune cells. This is quite a challenge and involves isolating individual cells and determining whether the antibody produced by each individual cell is an anti-cancer antibody. These antibody-producing cells only live for several days and then they are gone. This adds to the challenge of doing all of our procedures very quickly. Once we identify a cell that makes an anticancer antibody we need to trick another cell that does grow well in the lab to produce that antibody. This involves making a copy of the immune cell genetic code for that special anticancer antibody. Then that genetic code is inserted into another cell that will grow and make antibodies for us. We hope that we can rapidly surmount these last few hurdles to bring this treatment to patients and make their cancers disappear.