Personalized Cancer Vaccines to Conquer Cancer

A Q&A with Parker Institute Scientist Catherine Wu, MD

Catherine Wu, MD, a Parker Institute for Cancer Immunotherapy investigator and oncologist at Dana-Farber Cancer Institute, is one of the world’s foremost experts on cancer vaccines. In 2017, she published a seminal paper showing that a new type of personalized cancer vaccine works, keeping four of six skin cancer patients cancer-free after two and a half years.

These new vaccines are based on neoantigens, protein fragments specific to cancer cells. When given as a vaccine, these neoantigens can act as a flag to the immune system and cause it to attack the tumor. We sat down with Dr. Wu to learn more about this new therapy and how it can help cancer patients.

How did you get into studying cancer vaccines?

I’ve always been interested in the concept of curing cancer. My background is in stem cell transplant in patients with leukemia. Over time, this led me to ask what were these antigens that could stimulate an effective anti-tumor immune response, even in the absence of a transplant?

My earliest work in the area of vaccines was using whole tumor cell vaccines to treat leukemia. This was almost 15 years ago. Fast forward to now, and it’s a very exciting time, especially with what’s happening with personalized cancer vaccines.

How do neoantigen cancer vaccines work? 

In general, the idea behind a vaccine is that it stimulates the immune system to spotlight the particular antigens we want to target, creating an immune response.

A personalized cancer vaccine is engineered so that it can stimulate an immune response against an individual’s cancer cells. These tumors display certain antigens. These person-specific tumor antigens, what we call neoantigens, arise from mutations in that individual cancer. These days, with the lowering cost of sequencing, we can now search for neoantigens that are specific to a person’s own tumor and help the immune system work more effectively to search for and destroy tumors.

Because these mutations are not present in normal tissue, the vaccine should not generate major side effects against normal tissue.

The other thing that people need to understand is that even though people might have a particular type of cancer – say bladder cancer or lung cancer – one person’s lung cancer may be very different genetically from someone else’s lung cancer. So information about the mutations of each individual cancer allows us to personalize how we train the immune responses using a vaccine.

There have been cancer vaccines before. How are these new kinds different?

In the eras before, there was a tendency toward testing one-size-fits-all vaccines. In fact, the vast genetic variation among cancers means that having a one-size-fits-all treatment is not an effective strategy, which we have seen.

What we’re proposing is a personalized vaccine, generated on demand. In fact, when we create these new vaccines, we’re actually targeting 10, 15 or 20 neoantigens, not just one. It’s truly personalized.

What is also different now is that we have more tools at our disposal. Having many different prongs of attack against the same cancer is actually very important, because this acts as insurance against the cancer cells escaping the immune system and not responding to immunotherapy treatment.

We suspect that vaccines will likely be the most effective if coupled together with agents such as checkpoint inhibitors that release the brakes on the immune system. We saw in our study published last year that for those who had a relapse, adding checkpoint inhibitors then led to durable complete remission, lasting more than a year and a half later.

There are now handheld sequencing devices and new modes of delivering health care. In the future, a person might be able to walk up to a clinic, get sequenced and then in a relatively short amount of time have a vaccine made for them. Is that scenario far-fetched?

I don’t think it’s that far off in the future. With the advances in sequencing, we could very well see that happening sooner than you would think.

What about dendritic cell vaccines?

I think that’s a very exciting direction to go. We all know that dendritic cells, as antigen presenting cells, are very potent. If fed the right antigen, they can do a successful job at helping eradicate tumors. Our colleagues, like Nina Bhardwaj [a Parker Institute investigator at the Icahn School of Medicine at Mount Sinai], have already streamlined ways to get dendritic cells to be used in clinic. It’s still very specialized, but it’s a very important modality we need to test.

Dr. Wu is a member of the Parker Institute’s Tumor NoantigEn SeLection Alliance project to create effective personalized cancer vaccines for patients. 

This has been edited for clarity.