This excerpt comes from last week’s recorded interview with Keerthi Shetty, Senior Manager of Strategic initiatives at the Center for Personal Cancer Vaccines at Boston’s Dana Farber Cancer Institute. She talks about her team’s research and ground-breaking development off a vaccine for cancer. Listen to the complete audio conversation at embarkthepodcast.com.
LS: Hi Keerthi. Thanks for joining us today. Tell us a about your work with Dana Farber.
KS: I serve essentially as a program manager and liaison – the glue that interfaces with the scientists, the clinicians, regulatory people, legal folks, finance team, to make sure we’re all aligned in getting towards the goal of treating patients with these personal cancer vaccines.
LS: [During Covid] talk about vaccines…is ubiquitous…in the news, among pharmaceutical companies and in the political landscape. But we hear little about a vaccine for cancer patients. Would you take us through your work at Dana Farber? And if you can, tell us how close you might be to developing a cancer vaccine?
KS: A Cancer vaccine…was tried in the 80’s or 90’s without much success. Now with the advent of sequencing technology in genomics and better understanding of our immune system, we’re at the nexus of all this technology to really move forward with these cancer vaccines. Like the Covid vaccine, the cancer vaccine concept is based on the infectious diseases. The thing is, for these cancer vaccines that we’re working on, it’s not a prophylactic.
When you get a flu shot, it prevents you from getting the flu. This is not the case with our vaccines, which is therapeutic. You would administer it to a patient who’s already in stage three, or stage four. Now there are some cancer vaccines where you take it as a prophylactic, like the HPV cancer vaccine. I just want to clarify that is not the case with [NeoVax] our vaccine.
LS: In the past, many treatments for cancer have been great for killing cancer cells, but they also can kill healthy cells. Is there something about this vaccine that prevents that from happening? Does it keep the healthy cells untouched and vibrant?
KS: There are three pillars for treating cancer: surgery, radiation therapy, chemotherapy. And the fourth one that has emerged in the past decade or so is immunotherapy, in which you’re harnessing your own immune system to target cancer cells. It does have an impact on many patients, but still a good majority do not respond to them and there are some toxic side effects.
With personal cancer vaccines, we are targeting Neo (new) antigens that are specific to that patient and the tumor. They’re normally not found in healthy cells. So, antigens provide markers on the cell to say ‘okay, target me’ to the patient’s immune system. So, we’re using those new antigens in a truly personal matter, since they are so unique to that patient. With sequencing, we’re able to identify them, and select the optimal ones that we think would be immunogenic, which means they would elicit an immune response. In making it targeted and specific we hope that it would reduce any other side effects. In two trials, we haven’t had any toxicity or adverse events, serious adverse events, and we hope maybe the vaccine alone would be beneficial, and perhaps in synergy with other immunotherapies that make a stronger and more targeted response.
LS: As personal vaccines, does that mean they’re almost customized for that person? And for that person’s particular type of cancer?
Yes, exactly. It’s different for each patient. As you can imagine, that can be expensive. One of the challenges is manufacturing, because we had to make a new vaccine for the patient. And the vaccine format could be a peptide, which is a protein based, or it could be RNA based, which is what actually the COVID cancer, sorry, the COVID vaccines are right now. And the two key players in that Moderna and BioNtech, are actually cancer vaccine companies as well. So, a lot of technology is similar. But with the COVID vaccines, of course, you’re not being personally, the here, the manufacturing and, being able to scale is a bottleneck that we are experiencing, but we are coming up with technologies to try to address that.
LS: There’s so much expense in producing a one size fits all type of vaccine, but these are customized, which is, it’s really hard to wrap my head around how that can happen. Then there’s the matter of scalability. How much can you scale, [these vaccines] if you personalize them?
KS: Some groups that are, looking at shared antigens to see if we can make an off the shelf thing. So, multiple groups are working on some aspect of this. We already have two trials that we completed. And these are like phase one, pilot trials. And unlike some of the industry companies, we really focus on studying the patient…really studying what happens to the immune cells and kind of tracking the kinetics and how they change, in the body as over time after getting the vaccine. And I’d also like to note that, it’s the advent of sequencing technology and better understanding of the immune system that really has brought us to this point, and under technology that really has pushed us forward is, machine learning. And so, we actually use machine learning algorithms to predict the new antigens as well, that would be immunogenic. That’s how we select for the new antigens. And so that’s been an exciting research area of focus as well.
LS: What results do you hope to get given this is not a cure, but a treatment?
KS: We’re focused on stage three and stage four patients. So, in our portfolio, we are treating melanoma, glioblastoma and renal cell carcinoma patients with kidney cancer and will soon open trials in ovarian and blood malignancies like CLL and follicular lymphoma,
LS: What type of a result could a stage three or stage four cancer patient hope to get after receiving the vaccine?
KS: We’re hoping…to see if an immune response is activated. Hopefully that would translate to a better outcome or a benefit to the patient. But of course, yeah, definitely not going for a cure [but] the patient’s lifespan would increase a little bit compared to standard treatments for that indication.
Right now, it’s just more about understanding how this works in the patient in the body, and what their responses are. We would leave it to industry to kind of continue phase two and phase three trials with a larger sample size. And of course, there’s a lot of companies and institutions involved in this field as well. So, it’s just been a lot of progress has been made.
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