Breakthroughs in Vaccine Therapy for Cancer

M. D. Anderson Cancer Center

Cancer Newsline Audio Podcast Series

Date: June 01, 2009

Duration: 0 / 16:31

 

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Lisa Garvin:

 

Welcome to Cancer News Line, a weekly podcast series from the University of Texas, M.D. Anderson Cancer Center. Cancer News Line helps you stay current with all the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today in this Breaking News Edition we'll be talking about where we are in terms of cancer vaccines. This topic has garnered a lot of attention this week at the American Society of Clinical Oncology or ASCO which is the largest cancer conference in the world. Today we'll be speaking with two M.D. Anderson vaccine experts, both of whom are involved with prominent studies that were presented at ASCO. Dr. Patrick Hwu is Professor and Chair of M.D. Anderson's Department of Melanoma Medical Oncology and has been very involved with a specific melanoma vaccine since his tenure at the National Cancer Institute. Dr. Sattva Neelapu is Assistant Professor in the Department of Lymphoma Myeloma and was the principal investigator at M.D. Anderson of a vaccine for non-Hodgkin's Lymphoma. Both positive studies represent the first vaccine for their respective disease. Thank you both for joining us today.

 

Dr. Patrick Hwu:

 

Thanks Lisa.

 

Dr. Sattva Neelapu:

 
Thank You.

 

Garvin:

 

Dr. Hwu, let's start with you. Let's talk about vaccines in general. Give us a little background of vaccines and cancer care and how long we've been looking into them and how long it's taken to get where we are today.

 

Dr. Patrick Hwu:

 

I think to really look at the field you have to look at the field tumor immunology or strategies that stimulate the body's immune response against cancer. That's been going on for quite awhile. And all of these studies whether it's a targeted therapy or chemotherapy they all take time in order to determine their effectiveness in patients and there has been a slow but gradual progress over the years in stimulating the body's immune response against cancer. It started with cytokine therapy. Cytokines are natural proteins that the body's immune system makes that can stimulate immune cells. And there've been a number of cytokines that are actually approved for use in melanoma and other cancers such as interleukin 2 and interferon-alpha. And those cytokines do stimulate the body's immune response and have had some efficacy. Clearly though, the improvements are needed still with those approaches and so there've been a number of other technologies that have come along including T-cell therapy, growing T-cells from patients tumors that react against the cancers and infusing those. And those have also shown some efficacy. And there are cancer vaccines. Cancer vaccines are a way to stimulate the body's specifically T-cells in the body themselves that can recognize and kill the cancer. It's a way to stimulate those in the patient themselves to attack the cancer. And those studies are difficult because the body recognizes the cancer as part of itself. It's much harder to make a vaccine against a cancer because cancers come from our cells, compared to making a vaccine against a bacteria or virus which is very foreign. And so it has been a challenge. So that's why but there's been slow and gradual progress and that's why these studies are so exciting. Right now it's our first hint in a Phase III randomized study that there is some effectiveness of these cancer vaccines.

 

Garvin:

 

And it sounds like vaccines are actually the flagship of what we're calling personalized medicine now.

 

Hwu:

 

I totally agree. The T-cells or the immune cells recognize a very specific protein that is on the surface of cancer cells that identify them as a cancer cell. So it is a very personalized approach in that we use proteins that the patients cancer do express to try to use in a vaccine to stimulate the body's immune cells. And Dr. Neelapu's approach is especially personalized because they made a specific vaccine for each individual patient.

 

Garvin:

 

Let's talk about your study first. You were using metastatic melanoma patients. Tell me about your… it's a Phase II or a Phase III study?

 

Hwu:

 

It's a Phase III study. It's started with a Phase II study that was done in the National Cancer Institute in Dr. Steven Rosenberg's group where I used to work that showed some promise when we combined 2 agents that stimulated a body's immune response: interleukin-2 which is a standard FDA approved agent, as well as this GP-100 cancer vaccine. And it looked like when those 2 agents were combines, the response rates were higher compared to historical controls. But you have to be careful with historical controls because often times they don't reflect true differences. And so, you have to do randomized studies, taking the same population of patients and randomizing them to the vaccine or not. And so that's what was done in a multi-center study that was led by Doug Swarchentrooper who was my colleague at the National Cancer Institute who is now in Goshen, Indiana. He got a number of groups including M.D. Anderson to participate in a study randomizing between interleukin-2 by itself in patients with advanced melanoma compared to interleukin-2 plus vaccine. And it looked like from the results that the patients receiving the combination of interleukin-2 plus vaccine, had over twice the response rate from about 9 point 7 percent response to 22 point 1 percent response. So it's one of the first cancer vaccine studies that are positive.

 

Garvin:

 

Have you been able to predict survival at all in these groups? I mean the study is pretty brand new so you haven't been able to follow the patients for very long after the study, correct?

 

Hwu:

 

Well the study's actually taken a number of years to do so we do have some of that data and there is a statistically difference in the progression free survival: that's how long the patient survives before the cancer recurs. There's a trend towards an increase in overall survival, but that wasn't at the statistically significant level that we usually use of 5 percent P-value.

 

Garvin:

 

And as far as metastatic melanoma - from what I know - there are very few treatments available for advanced metastatic melanoma so this is potentially a new therapy that could really help a lot of patients?

 

Hwu:

 

That's a very good point. Currently the FDA approved agents for patients with advanced melanoma are only decarbazine and interleukin-2 as a single agent. And neither of those is adequate to treat the majority of patients. And so this does represent a significant advance. Still I think that we have now even newer agents that can't we can combine with this approach to make hopefully in our follow up studies make this response rate even better.

 

Garvin:

 

Great. Dr. Neelapu let's talk about your study. It's the first in its field and the findings are very significant and yours is extremely personalized because you're actually using the tumor itself to create your vaccine.

 

Dr. Sattva Neelapu:

 

Yes that's correct. So unlike the melanoma study that you just heard from Dr. Hwu, the vaccine formulation that we used in our lymphoma study is isolated protein from the patient's own tumor. So in a way it's a very personalized medicine because it is very specific to the patient's tumor and targets the patient's tumor. So this vaccine formulation was first tested in clinical trials almost 20 years ago when and subsequently a number of different groups including ours while we were at the NCI have shown that this vaccine formulation can induce anti-tumor immune responses in the majority of the patients with lymphoma. But as Dr. Hwu mentioned, it is difficult to assess the true benefit to the patients in Phase I and Phase II trials. So the randomized Phase III trial that was sponsored by Biotest and presented this week at ASCO, for the first time conclusively showed that this vaccine can induce meaningful clinical benefit. So what we observed on this study is that the patients who received the vaccine stayed in remission longer on an average by about 14 months as compared to the control group that received a nonspecific immune stimulant. So this result is very significant and it is the first successful therapeutic vaccine trial in patients with lymphoma.

 

Garvin:

 

Let's talk about standard treatments. We'll back up just a little bit: talk about standard treatments currently for non-Hodgkin's lymphoma. What currently are the standard treatments for NHL?

 

Neelapu:

 

So in non-Hodgkin's lymphoma there are a lot of standard chemotherapy agents that are quite effective in getting the complete remission. But the patient population that we targeted in this particular study is a subtype of non-Hodgkin's lymphoma called follicular lymphoma which is an indolent non-Hodgkin's lymphoma.

 

Garvin:

 

Slow growing.

 

Neelapu:

 

It's slow growing. So the natural history of this patient is that it's a very slow growing tumor, though it can be controlled for many, many years but it almost always comes back at some point in the future. And it is currently considered incurable. So at some point this patient's of options even though there are multiple therapies that can potentially work, at some point they run out of options and that's why we need additional modalities of treating these patients in the future.

 

Garvin:

 

Talk about the design. You said that there are several different components to this vaccine including the protein from the patient's own tumor.

 

Neelapu:

 

Yes so the specific vaccine which these patients receive actually had 3 components. So there is the idiotype protein which is a protein that we isolate from the patient's tumor. There's protein called KLH or keyhole limpet hemocyanin which is derived from shellfish. And there is a third component which is a cytokine or growth factor called GM-CSF which can stimulate the immune system. So the purpose of the idiotype protein is target the tumor. The purpose of the KLH is to act as a carrier molecule in order to present the idiotype protein as a foreign substance to the patient's own immune system. And the GM-CSF is thought to enhance the immune response KLH complex.

 

Garvin:

 

Tell me about your results among you said you had 117 that were randomized to the vaccine. Yeah, explain your results of the trial.

 

Neelapu:

 

So there were a total of 234 patients that would enroll on this trial and out of the way that this trial was designed is the patients initially are treated in a state of complete clinical with standard induction chemotherapy. And the regiment that we used is called PACE chemotherapy. And once they achieve a complete clinical they get randomized specific vaccine or the control nonspecific immune stimulant. And the nonspecific immune stimulant consisted of 2 components: the KLH and GM-CSF but we the idiotype protein isolated from the patient. So out of the 117 patients that got randomized in a 2 to 1 manner, for every 1 patient that got randomized to the control arm, there were 2 patients who got randomized to the specific vaccine. We observed the patients who received the vaccine stayed in remission longer after chemotherapy plus vaccine as opposed to the control group which got the chemotherapy plus control nonspecific immune stimulant.

 

Garvin:

 

And either one of you can answer this question. We haven't talked about side effects. What sort of side effects do you see in vaccine or personalized therapies like this?

 

Neelapu:

 

So in our vaccine formulation it was very well tolerated. So this vaccine caused really local skin reactions in terms of there could be some redness and some warmth which can persist for 3 or 4 days. After that it subsides. And the patients really don't have any major toxic side effects.

 

Hwu:

 

Similar for the melanoma vaccine in that mostly local swelling side effects but very well tolerated. Most of the side effects in our study were due to the high dose interleukin-2 which was given in combination.

 

Garvin:

 

Now do you think that you know -- there's a question here that says, "Shouldn't all patients be vaccinated for their cancer?" But I guess we're not quite there yet but perhaps we're taking steps in that direction?

 

Hwu:

 

I think one day we'll be able to utilize vaccines to try to prevent recurrences in patients who have their initial tumor resented. In melanoma that's the vast majority of patients come and we can cut out the initial tumor and patients are free of disease for all we know, but many of those patients do end up recurring depending on the nature of their initial lesion. And in that stage we can then potentially use vaccines to try to prevent the recurrence, but those studies take a long time because large numbers of patients need to be randomized and then followed for many years. And so those studies take a long time. But I think cancer vaccines also can play a role as we showed in these studies in more advanced settings, but probably will need to be used in combination with other agents.

 

Garvin:

 

And as we're wrapping up our Cancer News Line today, let's start with you Dr. Hwu. Where do we go from here with your study?

 

Hwu:

 

I think both of the these studies demonstrated that the immune system can be an important component of cancer therapeutics and I think in the future we need to combine with additional agents that we showed here that a combination was important of interleukin-2 plus the vaccine, but now there are a number of other agents that are very exciting, very promising and we can then incorporate them into follow-up iterations of this vaccine.

 

Garvin:

 

Dr. Neelapu, the next steps for your study and your research?

 

 

 

Neelapu:

 

Yes, so I agree with Dr. Hwu's comment on that we need to do combination chemotherapy -- combination immuno-therapies with the vaccine but I think in the case of the lymphoma study, there are a couple of other issues. So one, in parallel with our trial there were 2 other trials that were also conducted: randomized Phase III trials with lymphoma, one sponsored by Janet and a second by Pharell. And the main difference between these 3 trials is on the study which is the trial we talked about earlier the patients received the vaccine only after they achieved a complete clinical remission: in other words they were in a state of minimal disease. Where the trials not every patient was in that state of complete clinical remission prior to vaccination. And all 3 trials used a very similar idiotype vaccine formulation. But the trials results were released within the last year and they did not show any significant benefit to the patient. And one potential reason may be that because these patients have received their tumors at the time of vaccination and these tumors probably produced immunosuppressive factors that may have suppressed inhibited the immune responses and used better vaccine and rendered the immune cells ineffective. So in the future I think one may need to combine these vaccines with other agents that can block these immunosuppressant factors produced by the tumor in order to get the more effective clinical responses, especially in patients with a particular bulky tumors.

 

Garvin:

 

Great, thank you both. This is very exciting research and I wish you well at ASCO. If you have questions about anything you've heard today on Cancer News Line, contact Ask M.D. Anderson at 1-877-M.D. Anderson-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer News Line. Tune in next week for the next podcast in our series.

 

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