#21 – Cancer Vaccines: How the Immune System Learns to Recognize Tumors

00:00:06: And then their immune response to the vaccine and to the tumor was monitored.

00:00:12: The research team there found that eight of the sixteen made a T-cell response.

00:00:17: so they had a response for the vaccine, but other eight did not.

00:00:35: Hello and welcome in this week's episode of Virological!

00:00:49: This was recorded on June twenty ninth of twenty twenty six in Vienna.

00:00:54: Today we're going to talk about vaccines, but actually not about vaccines against infectious diseases.

00:01:01: We are going to be talking about anti-cancer vaccines and that's an interesting new development And there were a few publications That came out in the last months also in the past years and anti cancer vaccines have been in media quite a bit.

00:01:17: They wanted to shed light on their concept and then also discuss two different vaccines that have reported results relatively recently.

00:01:28: So for many types of cancers there are now good treatments, it's often a combination of surgery chemotherapy radiation And nowadays is also a lot of immunotherapy.

00:01:39: this could be antibodies That basically activate the immune response activate T cells.

00:01:46: This can be CAR T cells.

00:01:48: This could even be treatment with viruses that infect tumor cells and destroy them.

00:01:53: So all of these options are available right now for different types of cancers, and that has improved treatment and outcome tremendously.

00:02:01: but there's still some cancers that are hard to treat.

00:02:05: one of them is pancreatic cancer another one that is really hard-to-treat it very often unfortunately.

00:02:13: fateless glioblastoma that's a type of brain tumor, even melanoma although it got much easier to treat now is still very problematic disease.

00:02:24: And so I wanted to talk about this anti-cancer or antitumor vaccines that are in development.

00:02:31: these are therapeutic vaccine So they're given once somebody already has cancer and i'll get back to the concept you know in a minute.

00:02:39: but we have to differentiate them from prophylactic prevent cancer.

00:02:45: There's actually two of them that are routinely used, one thing against the human papillomavirus which can cause cancer in humans and another one is the hepatitis B virus which causes liver cancer in people.

00:02:59: And so these vaccines are prophylactic cancer vaccines while ones we're discussing today.

00:03:08: So as I said, i'm going to talk a little bit about the principle and then i am going to show or i m going to dog.

00:03:15: About two examples.

00:03:17: so what typically happens here is that there's surgery to remove the tumor could also be in some cases that just a biopsy staking but tumor material is used to basically develop the vaccine And it's going to be In all case vaccines that are specific for that person.

00:03:38: so it's personalized medicine.

00:03:40: that how you call this.

00:03:41: So basically material from the tumor is used and sequenced, typically regular tissue a healthy tissue is sequenced as well.

00:03:53: then these sequences are analyzed what often happens when a tumor forms?

00:03:59: There might be mutations, that may the causative reason for tumor formation.

00:04:06: And there maybe also additional mutation that occur in a tumor because tumor cells often mutate more frequently than regular cells and they grow so they can mutate it more.

00:04:17: So you have mutated genes of the tumor which means proteins are tumor-specific or tumor associated.

00:04:26: In a way, they are foreign to the rest of their body because in other bodies it doesn't exist.

00:04:31: We call them neo-antigens and that's what you're looking for when making an anti-cancer vaccine part of our natural body, right?

00:05:00: Now in some cases the body does that by itself.

00:05:05: The immune system does it by its self.

00:05:07: there might be a tumor cell that forms and the immune system recognizes it as foreign attacks it and removes it.

00:05:14: And There's never any cancer because the single tumor cells or a cluster of tumor cells is already removed before they're any signs of person being sick.

00:05:25: That's the best case scenario, and that probably happens in many people quite often.

00:05:31: But in contrast to that it can also be that there are two more forms... ...and the immune system doesn't recognize these new antigens sufficiently to suppress them.

00:05:41: And when I'm saying the immune systems very often this is a T cell response.

00:05:44: So T cells are immune cells.

00:05:46: they attack either infected cells or cells which have become malignant and remove them.

00:05:54: And so when cancer forms, often the T cells... The immune system is not strong enough.

00:06:01: Not targeted enough to actually remove the tumor.

00:06:04: So now for an anti-tumor or anti-cancer vaccine these sequences, this mutated sequence are identified and then they're basically usually the sections that mutate.

00:06:14: it are taking ...not the whole protein but just a mutated fragment.

00:06:19: They're stitched together in a row In an open reading frame, that's a protein encoding RNA in this case.

00:06:28: The RNA is synthesized and the RNA is formulated And it has been done very similar to mRNA vaccines That we have seen for COVID or other diseases.

00:06:38: If you immunize with that... ...the hope is that this vaccine induces now a strong immune response Specifically a T-cell response that targets the tumor because only the tumor has these mutated proteins these peptides that have the mutation in it.

00:06:56: Now, typically this vaccines are given several times and often when they're tested there combined with surgery or countermeasures treatment like immune therapy or radiation or chemotherapy.

00:07:12: And so first example I wanted to give is vaccine against pancreatic cancer.

00:07:18: Pancreatic cancer relatively deadly.

00:07:22: If surgery is performed to remove the tumor, typically the cancer recurrence comes back seven or nine months after the surgery in about ninety percent of individuals.

00:07:37: And what people often look here at it's a five-year overall survival after surgery and that if only surgeries perform this about eight to ten percent.

00:07:47: so very low survival rates.

00:07:50: If surgery is performed and then there are other treatments, the recurrence of the tumor can be slowed.

00:07:57: So typically it takes fourteen months for to come back but comes in about eighty percent of patients.

00:08:03: that's even when immunotherapy used or chemotherapy so on and so forth I use In this case overall survival still below thirty percent again not very high.

00:08:14: pancreatic cancer really a big problem.

00:08:17: And so in this trial, they focused on pancreatic cancer.

00:08:21: This was a small phase one trial.

00:08:23: it wasn't necessarily geared towards showing an effect with more geared towards looking at the immune response but I did see and affect...this is by the way typical for Phase One trial.

00:08:36: you're looking for safety or maybe for type of immunity induced But their not typically geared to control groups even if there's one.

00:08:47: And so this was done with a vaccine called AutoGene Cevumeran, which was developed by BionDec and the trial was conducted at Memorial Sloan Catering.

00:08:57: Which is really one of the prime hospitals in terms of cancer research but that's New York City!

00:09:06: In the end they had sixteen patients who initially got surgery to remove the tumor, then the tumor was sequenced by informatics.

00:09:18: Analysis were done and for each patient a vaccine was designed.

00:09:23: during that time they also...the patients also got immunotherapy.

00:09:27: They get chemotherapy And Then they got eight-to nine doses of this vaccine That was designed For each patient separately.

00:09:35: The immune response to the vaccine was monitored and the research team there found that eight of the sixteen made a T-cell response.

00:09:48: so they had a response.

00:09:50: And the other eight did not.

00:09:52: Now, they already did an analysis after approximately two years in which group didn't make their response.

00:10:01: They saw that there were recurrence after approximately thirteen months in, I think seven out of the eight patients.

00:10:10: So that cancer came back.

00:10:13: but for this initial two years they ate it had a response that responded to.

00:10:18: the vaccine actually has no recurrence and more recently paper came outward then looked four-four year outcome And six off day who mounted the response still were two or three.

00:10:35: two of them had developed cancer again, and one of them unfortunately died.

00:10:40: So seven out eight stayed alive.

00:10:43: six out the eight stayed tumor-free.

00:10:47: On the other side group that did not respond I mean basically same treatment but their immune system didn't respond to the vaccine.

00:10:55: Here five off eight were still alive after four years And it's better than at a typical treatment now.

00:11:04: Of course This is a small trial, and data from much larger trials are needed to look at the actual effect.

00:11:12: But for type of cancer that's as deadly as pancreatic cancer this actually pretty impressive data.

00:11:20: The second trial I wanted to describe was an entymelanoma vaccine.

00:11:28: It was a phase-to-be trial done in about one hundred fifty patients And it was performed in Australia and the US.

00:11:35: Larger trials are usually done in different clinics, often in different countries.

00:11:40: As I said this is a phase two B trial.

00:11:43: What we tested here was mRNA-Forty One Fifty Seven Forty Ones that know COVID vaccines.

00:11:51: If something starts with mRNA then means its made by Moderna.

00:11:55: So This Was A Moderna Vaccine That Is Tested & Being Developed Together With Merck.

00:12:02: So it was basically a very similar approach.

00:12:05: They also recruited patients in two thousand twenty one, then surgery was performed to remove the melanoma.

00:12:14: by the way this was stage three B Stage four melanoma that was looked at and these vaccines were formulated again.

00:12:23: This was done for each individual patient.

00:12:27: The highest number of neo-antigens included was thirty four.

00:12:32: So you can see that there is quite some mutations in these tumors.

00:12:35: and so, In this trial they had two different groups.

00:12:38: one group received an immune therapeutic monoclonal antibody checkpoint inhibitor And the other group received a checkpoint inhibiter monoclonal antibody plus the mRNA.

00:12:51: forty one fifty seven anti-cancer vaccine.

00:12:55: By the way, this vaccine is named in Dismaran autogene also because it's the genes from patients that are sequenced for looking for mutations.

00:13:11: and so what they found here is recurrence free.

00:13:14: survival was about fifty percent over five years in the individuals who got immune therapeutic alone.

00:13:25: And recurrence-free survival, over five year was seventy two percent of those who had gotten monoclonal antibody and immunotherapeutic and the vaccine.

00:13:36: so significant improvement here.

00:13:39: So recurrence free survival just basically means how many people the cancer came back.

00:13:44: You can also look at survival rates and they are better here for melanoma than for pancreatic cancer.

00:13:51: And so with the immune therapeutic alone, the survival rate over these five years was eighty-six percent.

00:14:00: If the immunotherapeutics were given together by the vaccine then the five year survival rate is ninety two percent.

00:14:10: Again this might not be as impressive what we have seen or what I've explained about the pancreatic cancer, but this is a larger study and its effect is pretty significant.

00:14:24: Also in this case the vaccine had to be given quite often that they were giving nine doses of the vaccine.

00:14:30: so i think some of these approaches are really what could save a lot people from cancer.

00:14:41: It's not clear how long it will take for these vaccines, for the therapeutic vaccines to get licensed but I think they are on a good way.

00:14:49: The problem currently still is that this is relatively expensive, as you can imagine.

00:14:53: You have to have surgery then there needs to be the sequencing of the tumor and a healthy tissue bioinformatics analysis And specifically for dead patient the vaccine was made.

00:15:04: Can't imagine it's not cheap.

00:15:06: at some point I heard but i'm no hundred percent sure if its actually accurate That costs about one hundred thousand dollars per patient.

00:15:14: But this again might change.

00:15:15: Technology gets better, technology improves and becomes cheaper And the hope is that at some point there may even be vaccines against cancer types like glioblastoma.

00:15:28: So it's really something that moving in right direction hopefully moves very fast.

00:15:34: That was for today from Virological.

00:15:36: I promise next time we're going to talk about viruses.

00:15:40: As always, if you have any questions concerns or comments please just write an email to Virological at podcastwerkstatt.com and If you like this podcast You can support us on steady.

00:15:52: Thanks for listening And until next time Bye!