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Using Cancer to Fight Cancer

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BOSTON ( Ivanhoe Newswire) - Measles, mumps and even the flu, they're just a few of the ailments that may come to mind when you think about vaccines. But now a new therapeutic vaccine 15 years in the making could make cancer kill itself.

Cancer flies under the immune system's radar in many cases remaining hidden until it's too late. Now a personalized vaccine developed in-part by Doctor David Avigan is helping fight the potential killer.

"The goal of the vaccine is to see whether one can really re-educate our immune system to see cancer cells as foreign, "Dr. David Avigan, Director of the Bone Marrow Transplant and Hematologic Malignancy Program at Beth Israel Deaconess Medical Center and Associate Professor of Medicine at Harvard Medical School, explained.

Still in the early stages of development, the vaccine fuses a patient's tumor cells with immune-stimulating dendritic cells. The new cells are then injected back into patients.

"What we saw was that there we very strong immune responses that were generated in these patients, against their own tumor cells," Dr. Avigan said.

In a phase one trial of the vaccine 66 percent of patients with advanced multiple myeloma stabilized for a period of time. In other studies, Doctor Avigan said some patients saw their disease regress. He also hopes to use the vaccine as a way to prevent recurrence.

Howard Bleich found out he had acute leukemia two years ago. After four rounds of chemo he was given the vaccine.

"The last time they checked me I had not relapsed," Howard said.

Howard's wife wasn't sure he'd live to see their twenty-fifth wedding anniversary. They've just celebrated their twenty-sixth.

Doctor Avigan said the vaccine could one day prove to be an effective cancer treatment that spares patients from the harsh side effects of chemotherapy. Phase two trials combining the vaccine with other medications are underway for acute leukemia, multiple myeloma, kidney cancer and breast cancer.

All the trials are currently enrolling. 

RESEARCH SUMMARY

BACKGROUND: Cancer is the general name for a group of more than 100 diseases. Although there are many kinds of cancer, all cancers start because abnormal cells grow out of control. Untreated cancers can cause serious illness and death. Cancer cells often travel to other parts of the body where they begin to grow and form new tumors. This happens when the cancer cells get into the body's bloodstream or lymph vessels. Over time, the tumors replace normal tissue. The process of cancer spreading is called metastasis.

No matter where a cancer may spread, it's always named for the place where it started. For example, breast cancer that has spread to the liver is called metastatic breast cancer, not liver cancer. Likewise, prostate cancer that has spread to the bone is called metastatic prostate cancer, not bone cancer. Different types of cancer can behave very differently. For instance, lung cancer and skin cancer are very different diseases. They grow at different rates and respond to different treatments. This is why people with cancer need treatment that is aimed at their kind of cancer. (Source: American Cancer Society)

VACCINATION NATION : Dr. David Avigan from Beth Israel Deaconess Medical Center has developed a personalized vaccine to fight cancer. The goal of the vaccine is to see whether a cancer patient can re-educate their immune system to see cancer cells as foreign, then go after them, attack them, and then kill off the disease. The vaccine fuses a patient's tumor cells with immune-stimulating dendritic cells. The new cells are then injected back into patients in order to reintroduce the entire tumor cell to the immune system so it will see it and go after it.

"We know that cancer has certain unique properties that are recognizable by the patient's own immune system and therefore are potential targets to fight against the disease. But we also know that cancer can find ways to avoid being recognized by the immune system," David Avigan, MD, Director of the Bone Marrow Transplant and Hematologic Malignancy Program at Beth Israel Medical Center and Associate Professor of Medicine at Harvard Medical School. "The goal of a cancer vaccine is to see whether we can re-educate the immune system to recognize cancer cells as foreign, and attack them in order to eliminate the disease." (Source: Ivanhoe Interview with Dr. David Avigan)

INTERVIEW

David Avigan, MD, Director of the Bone Marrow Transplant and Hematologic Malignancy Program at Beth Israel Deaconess Medical Center and Associate Professor of Medicine at Harvard Medical School, talks about a vaccine to fight cancer.

Can you talk about the cancer vaccine trial?

Dr. Avigan: We know that cancer has certain unique properties that are recognizable by the patient's own immune system and therefore are potential targets to fight against the disease. But we also know that cancer can find ways to avoid being recognized by the immune system. The goal of a cancer vaccine is to see whether we can re-educate the immune system to recognize cancer cells as foreign, and attack them in order to eliminate the disease.

This is done by taking unique proteins from the tumor and introducing them in a new way to the immune syste. Those cells, which are called dendritic cells, are "teachers" that tell the immune system what to go after and what to leave alone. Our particular approach has been to take patient derived tumor cells and fuse them together with these immune stimulating cells. We create what we call hybridoma or fused cell. This hybridoma now has all of the properties of the patient's own tumor along with the powerful immune-stimulating machinery of the dendritic cell. By doing this, we re-introduce the entire tumor cell to the immune system in a way that it can recognize. It also allows us to stimulate an immune response that targets the specific properties in an individual patient's tumor.

That seems to be the way that personalized medicine is going.

Dr. Avigan: There's a delicate balance in how the immune system works. It is designed to become activated in the face of foreign elements such as infections, but it also needs to avoid disturbing normal tissue. That's why using dendritic cells is critical; they can potentially activate the T cells that attack what is unique about the tumor and create a unique immune response, that, at the same time, leaves normal tissues alone.

We know that that when we take care of patients with malignancies, one of the challenges in using standard chemotherapies is that we are often attacking rapidly dividing cells. As a result, the treatment doesn't discriminate well between tthe normal tissue and the cancer itself. That's really the source of many of the unfortunate side effects that our patients have to contend with. Our hope is that by using a more focused vaccine we can educate the immune system to selectively go after the tumor and in that way create what we hope will be an effective therapy that doesn't cause the same kind of debilitating side effects.

What have the results been so far?

Dr. Avigan: This has really been a journey that started in the laboratory and made its way into the clinic. We've found that this combined cell that I described was extremely active in stimulating immune responses that were able to kill tumors in the test tube. We then went into a series of clinical trials to see what the nature of this effect was in real life when things are far more complicated than when you're designing experiments in the laboratory.

We conducted an initial set of what we call Phase I studies in whichwe looked at how the treatment's effects in terms of safety. Phase 1 studies also determine whether the vaccine generates immune effects.. This was done across a couple of different diseases including multiple myeloma, which is one of the blood cancers that we treat, as well as kidney cancer and breast cancer.

We saw very strong immune responses that were generated in these patients against their own tumor cells, and the vaccine appeared to be well tolerated [didn't cause troublesome side effects In patients with advanced disease we saw a group that showed some evidence of disease regression and a larger group inwhich the disease was stable for a long period of time.

After we finished the initial Phase I studies we then wanted to see whether the vaccine was more effective in combination with standard therapies in patients at an earlier phase of treatment. We recently completed a study of multiple myeloma patients who first underwent standard treatments including an autologous stem cell transplant (which is used to try and reduce the disease into a very low point of involvement.)

What we've seen so far is that we were able to make very strong immune responses against the patient's own tumor andthat some of those patients who had had a partial response to tregular treatment achieved a full response after additionally going through the period of vaccination.

Similarly in a study of patients with kidney cancer we saw that after they underwent the initial surgery to lower their disease volume, this vaccine was able to further reduce the disease. So that made us at least hopeful that this type of strategy could actually create an immune response that would have clinical efficacy and would be meaningful to patients.

What is the ultimate goal of the study?

Dr. Avigan: In our current studies, we are studying the combination of the vaccine with other agents that help bolster the immune system in patients with cancer. Specifically, we are examining whether an antibody that blocks one of the Immunosuppressive pathways known as PD-1/PDL-1 will enhance the response to the fusion vaccine.

How many studies are ongoing?

Dr. Avigan: There are several studies that are ongoing. We have been studying whether the fusion vaccine can stimulate immune responses that might prevent relapse in patients with acute myeloid leukemia. There is another ongoing study in patients with multiple myeloma in which we're combining the vaccine with an antibody that also works to stimulate the immune system. We are trying to hit the tumor from a couple of different angles. One, through the vaccine itself which educates the immune system to recognize that the tumor is foreign, and the other by using other aspects of the immune system to help amplify the response.

How long have you been working in this field?

Dr. Avigan: I have been working at this for more than fifteen years and a lot of recent advances that I mentioned have happened in the last five years. There has been a real acceleration of interest and trying to figure out ways to use the immune system in a more effective way against cancer. There has been a lot of excitement in translating new discoveries in this area from the laboratory into the clinical setting. I hope it will make a real difference for our patients.

What is it like to know you're on the cutting edge of benefiting so many people?

Dr. Avigan: It has particular meaning to me because I split my time between seeing patients in the clinic and trying to work on this in the laboratory and then in our clinical trials. I think we've learned a lot of humility in working with our patients, seeing their own sense of courage and perseverance in facing these difficult illnesses. There's still a tremendous amount that we need to learn and need to do better in terms of helping them; a lot of our therapies have made a big impact but there's a lot of room for improvement. I think we really feel that burden when we're thinking about patients that we have a connection to and thinking about how we can help them with the research.

Are they still accepting enrollments?

Dr. Avigan: Yes, the trials are actively ongoing right now.

Are there sites all over the country?

Dr. Avigan: The work that I mentioned is predominately being done here at Beth Israel Deaconess Medical Cente. We hope to ultimately conduct trials in multiple centers around the country because that's really how you definitively prove that a new therapy has real effectiveness. The results at this point are encouraging but we're still in the midst of fully understanding what they mean for our patients

What have been concrete results you've seen?

Dr. Avigan: In a Phase I study in patients with multiple myeloma we demonstrated that vaccination resulted in strong anti-tumor immune responses and disease stabilization in about two-thirds of the patients treated. In more recently completed studies we have demonstrated that vaccination enhances clinical responses in a subset of patients following stem cell transplantation. Several other studies are ongoing and we await their results. We will need to study this issue more to fully understand the long term implications for our patients.

With the multiple myeloma study, when you say two-thirds of patients, what do you mean by prolonged stability?

Dr. Avigan: Patients are monitored to see whether their disease is regressing, stable or growing. We have a series of perimeters that we watch. There were a group of patients that were followed who had multiple prior therapies in the past and their disease did not change for a prolonged period of time. The goal of those studies is not really to look at clinical response, it's to look at both safety and the immunologic response. For that we were able to show that their immune system [which we measure by looking at the T-cells the part of the immune system that recognize the tumor] have significantly expanded after the period of vaccination. In our most recent studies, we are examining the ability of vaccination to enhance clinical responses in patients undergoing initial standard therapy.

FOR MORE INFORMATION, PLEASE CONTACT:

Bonnie Prescott
Sr. Science Writer, Communications
Beth Israel Deaconess Medical Center
bprescot@bidmc.harvard.edu

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