Our next interview is with Dr Jay Berzofsky, Chief of the Vaccine Branch at NCI’s Centre for Cancer Research. He joined us at the Congress to participate in the Cancer and Immunotherapy Vaccines track, during which he explored triple synergistic combination immunotherapy. We are so grateful for Dr Berzofsky’s time and insights into cancer vaccine development and the challenges that come with it. We hope you enjoy the interview!
Introducing Dr Berzofsky
Dr Berzofsky kindly explains a bit about how his role works within the programme.
“We are government employees…we have nothing to do with grants for universities and so forth, but we do our own research.”
The branch is the vaccine branch, and they work on “basic science” and its applications to vaccines for HIV, cancer, and viruses that cause cancer, as well as COVID-19.
Triple synergistic combination immunotherapy
Dr Berzofsky kindly gave us a preview of his session the following day, which was to explore triple synergistic combination immunotherapy. He began by explaining that “there are different reasons why certain cancers may not respond well to immunotherapy”. He introduces “hot tumours”, those that are “inflamed” with T cells that “could kill the tumour cells”. However, the “tumour microenvironment” is “very immunosuppressive” and “prevents them from doing their job”.
“The T cells are there, but they need to be enabled.”
Next, Dr Berzofsky discusses “cold tumours”. These have no T cells infiltrating, often because the tumour doesn’t induce a good immune response. Essentially, the “immune system doesn’t see it as foreign”. These two different kinds of tumours need different strategies, suggests Dr Berzofsky.
“In the case of a hot tumour, you want to block the immunosuppression, to allow the T cells that are there to work.”
This is the case for melanoma, lung cancer, and a “number of other cancers”.
“In cold tumours, you need to generate an immune response, and that’s where the vaccine can come in.”
Inducing a T cell response that the “tumour itself failed to induce” converts the tumour from a cold tumour to a hot tumour. The vaccine, and the blockers of “negative regulation” such as checkpoint inhibitors, are synergistic!
“The vaccine can induce the T cells, but they won’t work if you don’t block the immunosuppressive environment.”
Initial challenges
Clearly developing therapeutic cancer vaccines is a challenging task. When we asked Dr Berzofsky about this, he reckoned that “there are a number of challenges!” A major challenge that he does discuss is the need to encourage the immune system to “reject” the cancer as it might a transplant. The immune system can be “exquisitely specific”, unlike an external approach like chemotherapy; it can “distinguish very cleanly” what is foreign in the body.
“But remember, the cancer cells are not foreign organisms like bacteria or viruses that are completely different from your own cells – they arose from your own cells.”
The target therefore, is a vaccine that can “train the immune system to see those unique differences”.
Further challenges
Another challenge that Dr Berzofsky identifies is that there are “many immunosuppressive mechanisms” beyond checkpoints.
“One has this panoply of suppressive mechanisms to overcome.”
We don’t have “really good ways” of overcoming these in humans yet, so Dr Berzofsky calls for research to “more effectively illuminate these other suppressive mechanisms”.
“It may be a daunting task to try to block 8 or 10 different suppressive mechanisms at the same time…so we need to find common nodes of intersection where some of these suppressive mechanisms interact, so we can block more than one at the same time.”
What more can be done?
As Dr Berzofsky has suggested, more work can be done, as always! We asked about potential areas for development that he can identify. Following from his previous answer, he emphasises the importance of finding “better ways, that are safe, to eliminate these immunoregulatory cells”. However, we also have to “strike the right balance”; they are there for a reason.
“It’s just going to take more research.”
Although we can make progress in animals, Dr Berzofsky suggests that the next step is “human clinical trials”.
Coming to the Congress
When we asked Dr Berzofsky about why he was joining us, he commented on the quality of his colleagues’ presentations!
“Hearing all the wonderful speakers that come to this meeting every year!”
Apart from the opportunity to learn, Dr Berzofsky was looking forward to meeting and developing potential collaborations.
“One of the things that’s important in science as in so many fields, is networking, because none of us can do everything in our own small laboratory.”
We are so grateful to Dr Berzofsky for his time and insights into some of the most challenging vaccine endeavours of our time. We hope to continue this conversation at future events. For more like this, make sure you subscribe to our weekly newsletters.
