It is my honor as one of TJ’s treating physicians at Moffitt Cancer Center, to have been asked by him to contribute to his “Patient #1” blog. I have been at Moffitt Cancer Center since 2006, first as a surgical oncology fellow in training and now as a faculty member specializing in surgery and immunology. During my training, I had witnessed, first-hand, the limitations of traditional chemotherapy as a treatment for cancer. While there is no question that chemotherapy has its place as a viable treatment option, the short list of problems with chemotherapy is:
- Chemotherapy is essentially a type of poison that indiscriminately kills dividing cells whether they are normal or abnormal, and this leads to side effects can be extremely difficult to handle,
- the treatment is generally only effective during the time the chemotherapy stays in the body, and thus chemotherapy typically requires repeated treatments to maintain a response, and
- even if cancer initially responds, the cancer cells all too often develop resistance to chemotherapy that was previously effective.
Despite these problems, chemotherapy can definitely lead to long-term benefit or even cures for some types of cancer, but unfortunately the cure rates for metastatic melanoma (ie melanoma that has spread from the spot of origin) are quite low. This has led to the development of alternatives to chemotherapy. One promising treatment is immunotherapy; a treatment that harnesses the body’s immune cells to attack the cancer as it would bacteria and viruses.
One of the ‘holy grails’ of cancer immunotherapy is to develop an anti-cancer vaccine, just as we have vaccines for diseases such as measles, mumps and rubella. Vaccines have a great track record against infectious diseases, as they have been used to eradicate smallpox off the face of the Earth, and a similar effort is underway for polio. It is much more difficult to use vaccines to fight off cancer, because unlike bacteria and viruses, cancer cells originally developed from our normal cells and still ‘look’ a lot like normal tissue to our immune system. Thus, cancer cells are not typically treated like an ‘invader’ by our immune system, even after vaccination. While cancer vaccines can be used to boost anti-tumor immune cells that can be detected in the circulation, they are either not numerous or powerful enough to cure most patients with melanoma. Ironically, it seems that cancer vaccines have the opposite problem as chemotherapy; while chemotherapy kills too much (ie both normal and abnormal cells), most of the cancer vaccines that have been used to date unfortunately do not kill enough.
To solve this problem, researchers at the National Cancer Institute (NCI), led by Dr Stephen Rosenberg successfully developed a work around. They noticed that when melanoma tumors are removed from patients, anti-tumor immune cells, called tumor-infiltrating T lymphocytes (referred to as ‘TIL’ below), can be frequently seen in the removed tumors. These TIL are not in high enough numbers to eradicate the tumors by themselves. The researchers at the NCI were able to explant patient tumors in the laboratory, and selectively grow these TIL using interleukin-2 (a molecule considered a type of ‘nutrient’ for T cell growth). They showed that the resulting TIL had relatively high tumor-killing activity and importantly did not kill normal cells. The researchers at the NCI used this ‘TIL cellular’ therapy as a new type of treatment. They showed that TIL cell therapy had the potential to selectively kill tumor cells, typically with less side effects compared to chemotherapy. Even more importantly, the TIL can also persist in the body for long after the treatment is over, which we like to call “the memory effect”. The treatment was shown to have a 50% response rate. More importantly, the treatment had a 20% complete response rate, and almost all the responses lasted >3 years.
While expensive and labor-intensive, the TIL therapy was successfully used at both MD Anderson in Houston, and Moffitt Cancer Center in Tampa. At Moffitt, we are collaborating with MD Anderson to try to boost patient responses with combination therapy. This effort has resulted in the trial in which TJ participated. The FDA recently approved a new form of immunotherapy called Yervoy, which is an stimulant that boosts immunity to cancer. Yervoy was proven to be better than chemotherapy in a large trial that received national attention, but despite this, unfortunately most patients who are treated with Yervoy still have disease progression.
It makes sense to combine Yervoy with TIL therapy. Yervoy treatment before the tumors are removed to grow TIL may improve the ‘quality’ of the TIL that are then grown in the laboratory. In our current trial, we then give the TIL treatment and continue the Yervoy after the TIL treatment, in order to boost the anti-tumor activity of the TIL treatment. This had never been tried before, and TJ was the very first patient to undergo the treatment (hence the “Patient #1 designation).
I would like to express my gratitude for TJ and other people like him afflicted by cancer. It takes courage to ‘volunteer’ for a treatment that has never been done before, especially for this type of treatment that can have all sorts of side effects we cannot predict. While some of his tumors have grown, I am hoping that “the memory effect” can still result in benefit for him.
I feel strongly that a single anti-cancer treatment by itself is usually not enough to wipe out cancer, but combination treatment, selected based on invidivual patient characteristics, is going to be the future of cancer treatment, and will lead to better results and even more cures.
T.J. Sharpe shares his fight against Stage 4 Melanoma in the Patient #1 blog. Read more »