Prostate Cancer Lab #29: Personalized Cancer Vaccines (Willy Hoos)

Advanced cancer patients with solid tumors see immunotherapies as offering one of the best paths to a durable response. Personalized cancer vaccines have a lot of potential because they offer a potential treatment option to nearly every cancer patient.

Willy Hoos is uniquely suited to lead a discussion on personalized cancer vaccines. He is the president of the Jaime Leandro Foundation for Therapeutic Cancer Vaccines, which provides access to personalized cancer vaccines; a Cancer Collaborator Lead for the 1440 Foundation, which is a health learning network enabling collaboration on cancer; and an advisor to xCures, which provides software and infrastructure services to identify and rank the most promising treatment options for people with cancer who have exhausted the standard of care.

What are personalized cancer vaccines and how do they work?

Personalized cancer vaccines can be used to introduce or stimulate selected T-cells (part of the immune system) to attack cancer cells. A personalized cancer vaccine leverages the immune system’s ability to see self/normal versus non-self/foreign cells and attack the non-self/foreign cells through a tailored antitumor response to their tumor mutation signature. The vaccine is trying to get your body to produce enough of the right T-cells, and then combine it with things like checkpoints or whatever makes sense in a given cancer in a given patient to make sure that those T-cells can do their job and win the battle against the tumor.

How are personalized cancer vaccines designed, manufactured, and administered?

The way we make personalized cancer vaccines is complicated. You sequence the tumor tissue and healthy tissue to identify mutations. Then there are a bunch of algorithms that can choose peptides (protein fragments) that match the mutations, their likelihood of binding to the immune system, their likelihood to be immunogenic, and other characteristics. The result is a list of potential peptides that could go into a vaccine. Then those peptides are manufactured and delivered by injections.

How effective are they?

The literature is evolving to indicate something is happening with these vaccines, but it’s certainly unclear that they work. There are ongoing vaccine-related trials in prostate cancer. There’s precedent that there’s some potential benefit in prostate cancer. The peptide vaccines, from everything that’s been seen, appear to be relatively safe. Most of the side effects are limited – similar to getting a flu vaccine or something where you get a sore arm, or you get a fever for a day or two. If you were to add checkpoint inhibitors, those have their risks.

What are other emerging immunotherapy variations?

There are other ways to amplify or enhance the behavior of the personalized vaccine approach. Tumor infiltrating lymphocytes (TIL) is where they take the tumor sample, find the T-cells that are in that sample and verify that those T-cells are the ones that are supposed to be there doing the job. If you just could boost those up in a variety of ways they would finish the job. Endogenous T-cell Therapy (ETCs) is taking the cells out of the blood and finding the T-cells that way. The hard part is now you’ve got billions of cells you’re sorting through, instead of 1000s, or hundreds of 1000s in the tumor sample, so you must have a better way of figuring out which ones are the right ones. T-cell Receptor (TCR) therapy is skipping finding a natural cell and finding a specific T-cell receptor.

How is testing evolving?

Sequencing costs are going down, yet the standard of care is still doing sequencing panels (checking 50 to 400 driver genes) for most patients. With whole exome sequencing (about 20,000 genes) you could get HLA typing (human leukocyte antigens tell your immune system which cells are self or non-self/foreign) for free, to possibly prioritize some TCR-type therapies that are out there. You create the option to do a vaccine. It may pick up some mutations that weren’t on the panel that turned out to be relevant, even though that’s rare. Why isn’t whole exome testing the standard of care

Who benefits most? How should this fit into a patient’s treatment strategy?

Most of the patients pursuing personalized cancer vaccines have been metastatic patients who are on various chemos, or have been on trials, and are trying to plan ahead, knowing that it takes three months to include this in one of their next therapies or to add it to their existing chemo regimen. Or if they have to take a chemo break, having the vaccine ready to boost their chances of something happening better than the known path.

One of the critiques of vaccines is that as a tumor gets larger, it starts to get more heterogeneous and more diffused and spread out across multiple sites in the body. The microenvironment is more suppressive to the immune system. Probably the less cancer you have, or the earlier stage, the better. Can it work in the later stage when a lot of patients start to turn their attention to something like this? There’s a case study of a patient with metastatic pancreatic cancer who had radiation and dual checkpoint inhibitors after they’d been on a vaccine for a couple of months, and they got a pretty profound response that’s ongoing and durable a couple years later. There are late stage examples, but it’s not clear. If you have a potential to respond to checkpoint inhibitors, and you don’t have time to wait one or two or three more months to get through the vaccine manufacturing, administration and waiting period, you want to try and get the benefit of the checkpoints because they have potential on their own. You must take the primary treatment goal first, and then the potential that that undermines some of the vaccine’s potential is just part of the risk.

And then there is the cost, and is it appropriate and ethical for a person or society to take on those costs? $80,000 is cheap for a cancer drug, if this were an approved drug.