How can we make better cancer vaccines?
Cancer cancer vaccine Cancer therapy

How can we make better cancer vaccines?

Dr. Talia Henkle
Dr. Talia Henkle

In 10 seconds? Many types of cancer vaccines have been developed to treat cancer, each with varying levels of success. Lessons learned from existing cancer vaccines have delineated key factors that drive success.

Wait, what’s a cancer vaccine? To start, in general terms, vaccines are scientific tools used to generate a specific immune response meant to prevent or help the body fend off disease. Vaccines were first developed to prevent infectious diseases (AKA prophylactic vaccines). As our understanding of the mechanics of how vaccines activate our immune system expanded, researchers started developing vaccines to treat diseases that have suboptimal immune activation, like cancer (AKA therapeutic vaccines). In sum, therapeutic cancer vaccines are treatments that generate a cancer-killing immune response–and are one of today’s hottest cancer treatment approaches.

How is a cancer vaccine different from a viral vaccine? Both types of vaccines work by getting immune cells to recognize and attack foreign or mutated elements, but the end-goals are different. Viral vaccines frequently aim to initiate a B cell immune response. B cells are the immune cells that produce antibodies, which can attach to viruses and block them from infecting our cells. Alternatively, cancer vaccines usually aim to initiate a T cell response. T cells are immune cells that can directly kill unhealthy cells–like tumor cells.

That sounds pretty straightforward. If only! Tumors consist of cells that have developed a slew of mutations that allow the cancerous cells to grow out of sync with the rest of the cells in our bodies. While these mutations cause tumor cells to develop some crazy properties, tumor cells physically and biochemically look a lot like healthy cells (much more similar to our healthy cells than a virus, for example). That means that cancer vaccines must be expertly targeted to only mutant features of cancer cells (AKA neoantigens).

Multiple aspects of cancer vaccine development (factors listed on top of bridge) need to be optimized and barriers need to be overcome (factors listed in 'troubled waters') before cancer vaccines can be counted on as a reliable cancer cure. Source: Sellars MC, Cell. 2022 Jul 21;185(15):2770-2788.

OK. Why does that make it tricky? Tumors develop, largely, from random mutations. As tumors grow and spread they develop new mutations, and thus new neoantigens. That means that a good vaccine target (AKA the neoantigen/ mutant cancer feature) for one patient might be completely irrelevant for another patient. This even occurs between different tumors within one patient. What's more, similar to viruses (*cough cough COVID), tumors can shapeshift over time to avoid vaccine-mediated immune attack, rendering the original vaccine ineffective. Furthermore, not all neoantigens are created equally. Some are great at activating T cells, while others are not.

So what can scientists do? Scientists have created algorithms and techniques that are getting better at detecting if a certain neoantigen will activate an anti-cancer T cell response or not. Additionally, they have already found multiple neoantigens that are common amongst many different cancer patients, lending hope that this approach could be generalized. But that’s only one of the barriers that needs to be overcome if a cancer vaccine is to work.

What other barriers exist? Our immune systems consist of many types of cells–some cells which launch attacks and immunosuppressive cells that turn those attacks off. Tumors enlist their own teams of immunosuppressive cells that can turn off any cancer-attacking immune cells. That means that these immunosuppressive cells must be deactivated if cancer vaccines are to work efficiently. To that end, a lot of research is focusing on how to tackle immunosuppressive cancer cells.

Can a vaccine be designed to overcome all these barriers? Never say never. But vaccines don’t need to do all the work themselves. Many experts believe that cancer vaccines will work best in combination with other cancer treatments, like checkpoint blockade therapies, chemotherapies, or other immune boosting therapies. The future for cancer vaccines is bright, but there’s a long road ahead as scientists work to optimize them.

Vaccine delivery

Intelligent vaccine design (AKA What should the vaccine be/look like?) is a crucial factor in leading to successful cancer vaccines. But vaccine delivery requires just as much optimization.

Vaccine delivery optimization may include asking questions like: How many doses are necessary? Does that change if used in combination with other treatments?  How should we select which patients should be offered the vaccine? Does the vaccine work better if it is injected into the muscle (like we do for viral vaccines) or directly into the tumor?

For cancer vaccines to see greater impact in the future, each aspect of cancer vaccination needs to be examined carefully!

Dr. Talia Henkle has distilled 4 research papers, saving your 14 hours of reading time

The Science Integrity Check of this 3-min Science Digest was performed by Flávia Oliveira Geraldes.

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