Breakthroughs in
Vaccine Therapy for Cancer
Cancer
Newsline Audio Podcast
Series
Date:
June 01, 2009
Duration:
0 / 16:31
Return to
Cancer
Newsline
Lisa Garvin:
Welcome to
Cancer News Line, a weekly podcast series from the
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
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.
Return to
Cancer
Newsline
© 2009 The University of
1515
1-800-392-1611 (