With Kevin’s treatment with the melanoma vaccine, I have had a lot of inquiries about how our vaccine was developed and about how Kevin was screened to be our first candidate for the vaccine.
Our vaccine project was one of many different areas of research I have been engaged in over the last twenty years. In my graduate school training in immunology at the University of Kansas Medical Center (1977-1981) I was involved in studies looking at the immunology of cancer patients. At that time, my research focused on aspects of the immune response when cells become cancerous. Specifically, I was involved in deciphering receptors on the surface of immune cells that would interact with cancer cells. My graduate thesis was a description of these receptors in patients with a type of blood cancer called Chronic Lymphocytic Leukemia (CLL). Since my completion of graduate work, I continued to have an interest in the immunology of cancer as I proceeded through my medical school training and the post-graduate clinical training that ensued. After joining the faculty at the KU med center I started to investigate the topic of the immunology of cancer. I was fascinated to learn that cancer patients had a completely intact immune system in most instances. The big question is why does cancer survive in the body in an environment where the body can recognize cancer cells?
One of the clues turns out to be that the immune system is unable to find the cancer cell in the body simply because there are millions of normal good cells in the body, like trying to find a needle in a hay stack. I conducted a series of investigations looking to see if the immune cells could be taught to easily identify cancer cells and direct them to the process of elimination of these abnormal cells by inciting an army of other immune cells to be commandeered to the cancer site. Along the way I deciphered the various rules that the body had for activating the immune system to destroy the cancer cells.
With the help of computer models we have been able to look at various proteins and peptides (short segments of proteins) that could be used in this activation process of the immune system to get an idea of what proteins would work in activating the immune system. The reason for using a computer-based approach is that we can exhaustively test thousands of proteins and peptides without having to do the laboratory work. After narrowing our search down to a few potential proteins, we then tested these in animal models. We used mice and subjected them to injections of cancer cells into their bellies and then challenged them with various vaccines that we developed based on our knowledge of their computer-based benefit. Our results were startling. Our experience with the animal model reflected our predictions based on our computer analysis. Armed with this information we refined our vaccine and in our final testing, we found 19 out of 20 mice survived the cancer challenge when given our vaccine. But, when offered other vaccines they succumbed to the disease.
Now we wanted to test this theory on patients, specifically those patients who had advanced melanoma and had exhausted all other treatment options including chemotherapy. To offer the vaccine to our first patient required a lot of careful screening. Because the vaccine had never been tested on a human being, we had to make sure all safeguards were in place. This included approval by the Human Subjects Committee and approval by the Food and Drug Administration for use of this vaccine on a compassionate basis.
Our first patient, Kevin, was no stranger to me. Kevin, now age 32, has been my patient for over ten years. When he was originally diagnosed with melanoma he had an abnormal mole in his left leg and he had surgery for it. Because this melanoma was aggressive, he also had a second operation that resulted in wide excision of the skin in the area of the mole. Additionally, the surgeons dissected the groin area to remove lymph nodes from that site. Unfortunately for Kevin, the melanoma had already spread to these groin lymph nodes. He had advanced melanoma. Kevin received a drug called Interferon that had been shown to be beneficial for melanoma patients. He spent an entire year receiving interferon injections every week. The treatments were not easy and he experienced many side effects including fever, chills and flu like symptoms.
With this treatment, however, Kevin was in complete remission and the remission lasted for ten years. Unfortunately, in the last year Kevin developed multiple nodules under the skin. Biopsy of a nodule showed that this was metastatic melanoma that had come back after ten years of being disease free. After extensive discussion with Kevin, we decided to proceed with chemotherapy. Kevin received six months of chemotherapy. We evaluated the response to chemotherapy every two months. Initially he did have a good response, but by the end of the six months of treatments, he had failed and was suffering many complications from the chemotherapy. He was losing weight, he was fatigued all the time to a point he could no longer work. He had changes in taste and he had no appetite. He had numbness and tingling in his hands and feet which is a side effect called peripheral neuropathy.
After completing six months of chemotherapy, Kevin needed a break from treatment. He needed to recover some of his strength, improve his strength and stamina. During this period, we worried about disease progression. Metastatic melanoma can spread to vital organs like the brain, liver, lungs and bone. We immediately set about to look for another alternative to chemotherapy treatments. After exhaustive discussion and review, I thought that Kevin would be a good candidate for the melanoma vaccine. Kevin was also enthusiastic about trying the vaccine. Because of the experimental nature of the treatment, the treatment was offered to him at no cost.
Kevin started his treatment on St. Patrick’s Day, March 17, 2008. The vaccine was administered by an intramuscular injection. The initial series of injections were given three times a week for two weeks. At each clinic visit wee exhaustively queried Kevin about potential side effects. The intramuscular injections did cause some pain. On the day following the injections, he did experience some low-grade fevers and some flu-like symptoms. He also experienced joint pain in the joints closest to the injections sites. We rotated injections so that different limbs were used and the joint pain would follow. With each injection we carefully measured the different tumor masses that we could feel under the skin.
Kevin started with five lesions and three have disappeared. The fourth lesion is continuing to shrink. The fifth lesion however, increased in size. This was puzzling to us. Because this lesion was in the armpit and close to the skin, we asked Kevin’s surgeon to excise the lesion. The pathology on this lesion is now available. The findings are that a large part of this lesion has necrosis (dead cells) and hemorrhage (bleeding). Only a very small part of the lesion is occupied by melanoma. Our inference is that this lesion with melanoma was also responding to the vaccine therapy. The reason we believe it appeared to be enlarging was the hemorrhage and necrosis. So far, all five of the index lesions with melanoma have responded to the vaccine therapy.
Kevin is continuing to undergo vaccine therapies, and we will provide further updates as they become available.
