Written By: Mericien Venzon

This new blog series will go ‘Behind the Paper’ for one of JRNLclub’s most outstanding recent uploads. Our intention is to highlight the often overlooked human element of the impactful science that our videos showcase and help younger trainees see parts of themselves in the scientists they admire.

In this first feature for January, Dr. Faezzah Baharom, a postdoctoral fellow in the Robert Seder Lab at the Vaccine Research Center at the NIH, sat down with JRNLclub ambassador Mericien Venzon. In their Nature Immunology publication, Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells, Dr. Baharom and colleagues excitingly show how IV delivery of Avidea Tech's cancer vaccine induces stem-like CD8 T cells, leading to superior antitumor control. (This interview has been edited for clarity.)

Your study has really important implications for cancer treatment. What excites you most about the findings of your study?

Well, through our study we had a way to really understand basic T cell immunology through our vaccine platform. On a bigger scale in terms of clinical relevance, we are actually moving forward with a clinical trial, and that is influenced by the knowledge gained in our study about how you can deliver vaccines in a different way and get even better responses. There's definitely a translational element to it that’s exciting. On a very basic level, it's an important tool for us to really understand how the immune system works. People have done that with infection models, for example, how T cells develop or go through the differentiation process by using infection model viruses like LCMV, but this is the first time that’s been done using a cancer vaccine in trying to understand how to overcome T cell exhaustion. A lot of the T cell work that has been done in the field so far has used transgenic mice, or mice that have TCR’s specific for a certain model antigen--like the commonly used Ova antigen-- but in our study we’re using a neoantigen, so we’re looking at primary responses and it's really cool to be able to show we can specifically generate stem-like T cells.

Were there any specific challenges you faced during this project and if so, how did you work through them?

It always starts with you having a hypothesis, and you think this is what's happening, and science is essentially about testing your hypotheses. For the story that we have published, there were a lot of other lines of arguments that didn't work out. And this is just the way Biology is! You can guess what is going on, but what you have, in this case, are the mice telling you this is what's happening and you try to understand why. With animal models you can at least eliminate one factor at a time. For example, you can deplete dendritic cells and see what happens then. The real challenge will be to try to translate it all to humans. I think that's the bigger challenge because we are so different. With cancer neoantigens, we're really thinking about personalized cancer vaccines because every person's cancer is different. We are working to get a treatment that addresses the differences between us and I think that's sort of moving beyond this paper. The challenge will be to try to find something that works well for more people, and eventually for everyone.

How did you first get interested in science?

I think it started in high school. I'm originally from Singapore and I had a fantastic biology teacher who made things easy to understand. I think it comes down to that. Your initial interest is from someone who makes something complicated seem accessible. Then in college I studied biological sciences and my first lab was an influenza virus lab. During my PhD, I was interested in how the immune system works to attack viruses and how you could really use that information to design better vaccines. You can approach cancer in a similar way and think of cancer as a foreign object, and use the things you've learned about how the immune system fights viruses to design vaccines that target cancer. I love that cross between different fields! I think immunology is very broad. Now we're even moving to using the things we know about tumors and how they suppress the immune system to work on autoimmunity and in that case, your goals are to dampen the immune system. Everything is related and if you have a good core of immunology, then you can apply it to a lot of different diseases and problems.

Do you have any role models?

There's a lot, but I think the immediate one that comes to mind is my mentor for my PhD, Florent Ginhoux. He’s an immunologist but when I talk to him, he often thinks about science as an artist. I think that's the part about science that's not something we think about as more junior people. We're trying to get this experiment to work. The details are important, of course, but I think at a bigger level, you have to be very creative in your scientific questions. I think you can end up being trapped in the details and small issues that you often forget to zoom out and think about the big picture. So for me, I'm very influenced by his sort of way of approaching science and zooming out to approach things differently. Even in the case of something well established, it helps to think about ways you can question it. And then you enjoy it! I feel like when you're working on art, it’s more enjoyable and a bit spiritual and you’re thinking about what's beautiful and what can give impact.

One last question. You mentioned you're originally from Singapore, being both a woman and a member of a group that's underrepresented in science and especially in academia, how has that experience been? Has it been positive or negative?

That's a tough question. I think I have almost developed a thick skin. If someone is criticizing me or is speaking over me I try not to think of it as personal. I never like to make it about my gender or my ethnicity or being a foreigner. I try to be very focused on the science and I think that's sort of a defense mechanism to survive in this world. I’m very aware of the ‘old boys club’, and it can be intimidating but the best thing you can do is reach out and see if you can establish networks and collaborate with other scientists in the field. Overall, I would say that I have not felt like it has been a negative experience but I'm very aware that there are systemic biases that make it harder for minorities. At the end of the day people respect good science, and I think you can go beyond your gender and focus on offering the most that you can intellectually.

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If you haven’t yet, check out Dr. Baharom’s JRNLclub video here: Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells

Mericien Venzon is a 5th year MD/PhD student at NYU School of Medicine in the lab of Dr. Ken Cadwell where she studies the interactions between the gut microbiota and parasitic helminths. She is also Founder and President of the Women of MSTPxNYU which strives to support and advocate for women in science and medicine.