New Steps Toward A Vaccine For Cancer

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Let’s do a little word association. What do you say? When you hear the word “vaccine,” what comes to mind? COVID, monkeypox, maybe polio, right? One word that does not come to mind I’m betting is cancer– cancer vaccine.

And while a cancer vaccine may not be grabbing headlines, my next guest is working on a vaccine that would target tumors that tend to be resistant to treatment, like melanoma, triple negative breast cancer. And so far, this type of cancer vaccine is effective in lab animals. The results of the research were recently published in the journal Nature.

Joining me now to tell us more about that is Kai Wucherpfennig, Chair of Cancer Immunology and Virology at Dana-Farber Cancer Institute. He is also Professor of Neurology at Harvard Med School. Welcome to Science Friday.

KAI W. WUCHERPFENNIG: Thank you, Ira. Glad to join you.

IRA FLATOW: Let’s start with the basics, should we? How does the immune system respond when it detects cancer cells?

KAI W. WUCHERPFENNIG: The immune system has a very sophisticated ability to detect trouble within cells that are within our body. The cells that are particularly relevant here are called T cells. These T cells have a special ability to detect proteins that are hiding with inside a cell.

I can explain this best in the context of a viral infection. So let’s say a cell is infected with a virus. A T cell comes along. It crawls over the cells and detects proteins that display small snippets of many proteins inside that cell. And when the T cell detects one of these snippets– we call them peptides– then the T cell becomes highly activated. It can kill that infected cell.

Now, you can imagine that in the context of cancer, these T cells can be very powerful, because they not only crawl through healthy tissue to detect any trouble, but they can also migrate into tumors and then detect abnormal proteins that are expressed by tumor cells and then kill those tumor cells.

IRA FLATOW: OK, so tell me about how this vaccine that you’re working on works to prevent cancer from spreading and continuing to mutate.

KAI W. WUCHERPFENNIG: The challenge with cancer vaccines, and actually any type of cancer treatment, is that tumors continue to mutate. This is similar to viruses, for example, the COVID-19 virus, which continues to mutate and therefore can evade an immune response. The same happens within tumors. Tumors generate a large number of mutations. And these variant tumor cells can escape immune detection.

And so what happens when T cells attack tumor cells, they rely on these proteins that can present these peptides from inside the cells. And when cancer cells mutate that process, the tumor cells become invisible to T cells. So this is the problem that we try to address.

And our hypothesis was that if we could generate a cancer vaccine in which there’s a multi-pronged attack against the tumor cells, not only by T cells, but also by other important immune cells, maybe it would be more difficult for those cancer cells to become resistant.

IRA FLATOW: And has that been successful?

KAI W. WUCHERPFENNIG: Yes. And so what we were able to do is to develop a vaccine that stimulates T cells and also NK cells. NK cells are Natural Killer cells and they have the ability to detect and kill tumor cells. Now, what is important here is that T cells and NK cells actually recognize cancer cells through different receptor systems. So it’s very difficult for a cancer cell to mutate in a way that it simultaneously evades detection by both T cells and NK cells.

IRA FLATOW: Now, we’re calling this a vaccine. Is that the true definition of what you’re working on? We normally think of vaccines as being prophylactic, something that’s preventative.

KAI W. WUCHERPFENNIG: Yeah, so these are therapeutic vaccines. And therapeutic vaccines are more challenging than prophylactic vaccines. For example, you get a flu vaccine before you get the virus. It is easier to prevent an infection than to deal with an active infection.

And the same applies to cancer. It is a much more difficult to treat with ongoing established disease that may be widespread than to prevent the disease. And that’s why it has been challenging to develop cancer vaccines.

IRA FLATOW: So do you give your vaccine, at least as you’re testing it now, after you discover cancer?

KAI W. WUCHERPFENNIG: Yes. So the way we’ve done this in our mouse models is that we actually mimic an important clinical setting. So the challenge in many cancer patients is that they have an initial surgery, the surgery is successful, but the tumor was already locally invasive. And frequently, there’s a little bit of something left, maybe 0.1% of the tumor, either locally or cells that have already spread.

And so what we did in our mouse model is to use tumor cells that are very aggressive and that spread very rapidly. We let the tumors grow to a substantial size. Then we performed surgery on the mice. And only after we had done the surgery did we deliver the vaccine. And what we found was that the vaccine was very effective in preventing the outgrowth of metastatic disease.

IRA FLATOW: Wow.

KAI W. WUCHERPFENNIG: This is how we envision cancer vaccines will be used in the future. So not waiting until the patient has a severe relapse with metastases in the liver and the lungs or in the brain, but actually giving a vaccine after surgery to prevent a recurrence.

IRA FLATOW: So this is immunotherapy, right? You’re tweaking the body to be able to search out any remaining cancer cells.

KAI W. WUCHERPFENNIG: Yes. This is definitely immunotherapy. And the concept of immunotherapy is to empower the immune system to do what it already does very well, which is to perform surveillance of the body at all times and detect cells that are stressed.

And so what we did actually with our vaccine is to target a stress protein that is frequently expressed by cancer cells because they undergo damage of their genome. And these proteins are rarely expressed by healthy cells. And so what cancer cells do is they actually evade this immune detection mechanism and they cleave this molecule off the cell surface. And our vaccine targets a part of the protein that prevents this evasion mechanism.

And the reason this matters for this combined T cell and NK cell attack is that these molecules are detected by receptors on both T cells and NK cells. So with this approach, we can actually trigger a combined attack by T cells and NK cells.

IRA FLATOW: Most people diagnosed with cancer, from what I understand, will undergo a few different treatments, right? How would this type of cancer vaccine work with the other available cancer treatments?

KAI W. WUCHERPFENNIG: Given that cancer is a very complex disease, we definitely want to have many different tools and then select those therapeutic tools that are most relevant for a given patient. So the vaccine we’ve developed is most relevant for patients who upregulate the stress proteins on the tumor cells. And those we can actually detect in the blood of the patients. It’s not a vaccine that we think would work in every cancer patient, but the pathway is relevant in the number of important cancers that are very common.

IRA FLATOW: Yes, and you’ve chosen some really deadly ones like melanoma and triple negative breast cancer.

KAI W. WUCHERPFENNIG: Yes, so we tend to work on the cancers that are challenges for conventional therapies because we think that immunotherapy has the potential to deliver long-term durable control of tumors. There is already substantial evidence that the immune system can do this.

You probably had people previously on your show who are working on immune checkpoint blockade which targets inhibitory receptors on T cells. And with those drugs, we have already seen that widespread metastatic disease can be controlled long-term with these drugs. But unfortunately, only in a subpopulation of patients.

IRA FLATOW: Now, I know this vaccine has only been tested in animals.

KAI W. WUCHERPFENNIG: Yes.

IRA FLATOW: And we’ve been doing this show over 30 years and we have heard researchers cure animals of all kinds of diseases, but when they try to apply them to people, they don’t work all the time. What are the chances that this will actually work in humans?

KAI W. WUCHERPFENNIG: Right. This is always the ultimate test. The way I think about cancer research is that we want to generate new ideas that can be tested in the clinic. And to develop successful cancer treatments, we need many shots on goal. I’m not going to be here claiming that our vaccine is going to be the final answer, but I think it’s an approach that is worth testing.

IRA FLATOW: And so when will the tests in people begin? Are you that close or close enough to see that end of the tunnel?

KAI W. WUCHERPFENNIG: Yes, so we are collaborating with a leading pharmaceutical company to take this to the clinic. And we anticipate starting testing in patient next year. I’ve actually been contacted by a number of patients. And I always, unfortunately, have to tell them that I will not be the one who will be able to select patients for trials.

The company that we work with will actually run the trial and they will select patients based on their criteria. This is really out of my hands. We develop the ideas and then other people take these ideas and take it to the next step.

IRA FLATOW: Other researchers are working to make vaccines that will actually prevent people from developing cancer using specifically tailored formulations. How can a vaccine prevent someone from developing cancer and how is your vaccine different from these other approaches?

KAI W. WUCHERPFENNIG: Yes, so the ultimate goal of the field, of course, is prevention. But prevention is more difficult because not everybody is going to develop cancer and you also don’t know which cancer– if somebody will develop cancer, which cancer they will get. They’re not all the same.

So developing generic cancer vaccines is a pretty substantial challenge, in part, because this vaccine would need to be associated with a very substantial safety profile. The way we think about our vaccine is that we want to give it to patients with cancer who have– as I said, they’ve had a successful surgery. They have a high chance that there is disease left. And at that point, we want to eliminate it using both T cells and NK cells as a multi-pronged strategy.

And I think this is an important way of thinking about cancer vaccines. Right now cancer vaccines are frequently given to patients with advanced disease who have metastases in many different organs. And as you can imagine, the more tumor cells there are, the more readily a few of these cells can evade an immune attack and then cause a relapse. So we like to target cancer when it’s down and when the tumor burden has been reduced more than 100-fold by a successful surgery.

IRA FLATOW: This is Science Friday from WNYC Studios. If you’re just joining us, we’re talking about a new type of cancer treatment, a vaccine, with researcher Dr. Kai Wucherpfennig. As I say, we’ve been talking about cancer vaccines for a while.

And I’m thinking, well, just about, what, 10 years ago, a decade ago, developing a cancer vaccine seemed pretty implausible. We talked about it, but it was always somewhere way down the road. Has there been a paradigm shift in the field of cancer treatment that now we can talk about it plausibly?

KAI W. WUCHERPFENNIG: Yes. So, Ira, this is one of the big challenges in biomedical research. So I would say, 15 years ago, we weren’t really sure that the immune system had an important role in fighting cancer. And we’re now confident about that. So I think we’re confident about the biology that we’re trying to manipulate.

And now we’re talking about the specifics. We’re talking about what antigens do you want to target? How do you formulate the vaccine? Which immune stimulatory agents do you want to use? And there are, of course, a lot of choices that the field needs to make when formulating vaccines and then taking them to clinical trials.

I do think that given our insights on the role of the immune system in cancer, that this will eventually be successful. I cannot tell you whether it’s going to be in five years or it’s going to take another 10 years, right?

[LAUGHTER]

IRA FLATOW: Yeah, I don’t expect you to.

KAI W. WUCHERPFENNIG: This is a hard problem.

IRA FLATOW: Let me get that as my last question here. It is a hard problem. What don’t you know that you need to know?

KAI W. WUCHERPFENNIG: So we know how to develop vaccines against infectious diseases. That field has matured for more than 100 years, right? But in infectious diseases, we’re trying to develop primarily an antibody response or antibodies that can neutralize, for example, a virus.

But in cancer, we actually need to induce a T cell response. And so the technical aspects of how you optimally induce a T cell response and endow these T cells with optimal cancer-fighting abilities, that is more complex. And it is at the intersection of the biology and immune engineering.

And there are a lot of details that are very important in developing these vaccines. And that’s a very active field. And I do anticipate that the field will make progress. But as I said, I can’t give you specifics on the timeline.

IRA FLATOW: Well, Professor, I want to thank you very much for taking the time to be with us today.

KAI W. WUCHERPFENNIG: Thank you, Ira. A great pleasure for me.

IRA FLATOW: And good luck to you and your research.

KAI W. WUCHERPFENNIG: Thank you very much. Bye-bye.

IRA FLATOW: Dr. Kai Wucherpfennig, Chair of Cancer Immunology and Virology at the Dana-Farber Cancer Institute and he’s also Professor of Neurology at Harvard Med School.

Next week, we’re going to be continuing our conversation about the latest in cancer treatment. We’ll be talking about CAR T cell therapy, which is also based on recent advances in our understanding of the immune system. And people are talking about this very, very positively. We’ll tell you why.

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