Dr. Ferdinando Pucci: Unlocking Our Immune System to Fight Cancer

Over the past few years, the public has had a crash course in learning how many vaccines work to prepare our immune systems to tackle new diseases. In the world of cancer research and treatment, immunotherapy has a similar goal – to boost the body’s own immune response in fighting the disease. In fact, many immunotherapy treatment are considered “therapeutic vaccines”.

DocWire News spoke with Ferdinando Pucci, PhD, whose previous research suggests that antibodies against tumors are present for a short time when cancer initially appears in the body. Now, he is determined to learn how antibodies against tumors are made and use this knowledge to develop safe vaccine therapies to cure existing disease – specifically cancer.

DocWire News: Can you give us some background on yourself?

Dr. Ferdinando Pucci: Yeah, sure. My name is Ferdinando Pucci. I am Assistant Professor here at OHSU in the Knight Cancer Institute. I grew up in Italy, was raised and born, did my PhD in Milan in the laboratory of Michele De Palma and Luigi Naldini. They are better known for gene therapy and genetic engineering, so that’s what I learned. I took that expertise with me from a postdoc in Boston at Harvard Medical School, in the laboratory of Mikael Pitte and there we had a lot of fun trying to figure out new approaches to investigate these so-called extracellular vesicles in vivo, in the native environment.

I did a short stint after my postdoc in biotech. Boston is the world biotech capital, so it was almost impossible to avoid that. I got into a small startup. I think I was the third employee, and that was a great experience. Taught me a bunch about translating research for clinical applications and it also introduced me to the world of T-cells. After that, I started applying for faculty positions and I was lucky to be recruited here at OHSU by [inaudible] Cousins and Dr. Flint, the chair of the Otolaryngology department. And here I am.

Talk to us about immunotherapy, and how it’s changed cancer treatment?

Probably as you know, and most of our audience know, there is lot of excitement about immunotherapy. It’s a breakthrough therapy. We are starting to talk about cure cancer. There is a Nobel Prize, two Nobel Prizes actually, that have been awarded to well-deserved scientists that pioneered this field. It is not just about the Nobel Prize for their achievements in the so-called checkpoint blockade therapy, but it also a lot of gene therapy approaches with CAR T-cells that enable the high numbers, high fractions of patients with the liquid cancers, like lymphomas, to be cured. With solid cancers, the situation is still promising, but is not as good as with liquid cancers. The cure rate, the complete response rates for solid cancers in patients treated with immunotherapy is still 10%, 20% range. So there is a large margin of improvement.

Talk to us about the Pucci Laboratory, and the research you’re conducting.

My laboratory investigates… The main theme of the research program is the role of extracellular vesicles in cancer, both in relation to immunotherapy and with early detection. Extracellular vesicles, as you may know, are kind of a small particles, membrane bound particles, that pretty much every cell type releases. Tumor cells although release much higher numbers of these particles. And this is a very interesting phenomenon because the role that may have in communication between tumor cells and host immune cells, other host normal cells. This communication is fundamentally different from the traditional communication that we all study in textbooks, for example, in which you have a one single, signaling element that is released by one cell and sensed by another cell, either locally or a distant, in a distant place. Extracellular vesicles carry multiple signals, clustered on a very small surface. So whether these signals are all of the same type or they also integrate different signals, this is something that communication via extracellular vesicles can achieve.

It’s really not clear what the consequences is of these abilities in communication are, especially in vivo where these extracellular vesicles are very difficult to study. This is where my lab is starting to make headway. Basically, we develop the models, genetic models, to avoid touching and isolate these vesicles in vitro and then reinfuse them into animal models. So we just track them how they are in vivo. If you wish, this type of communication mediated by extracellular vesicles is like a Web 2.0. So it is really the next generation, the next level of our understanding in how intercellular communication works.

We are applying these, as I said, in the context of cancer early detection and immune response to cancer, because these extracellular vesicles carry tumor antigens. As you may know, tumor antigens are very popular now too. They’re a focus of a lot of research to understand how we can use tumor antigens, tumor neoantigens, to better target even solid tumors with immunotherapies.

You received a V Scholar Grant from the V Foundation. Can you talk to us about the significance of that?

Yeah, I’m really grateful for the V Foundation for funding this research. It’s focused on developing therapeutic cancer vaccines. As you may know, cancer vaccines are another hot topic in immunotherapy. The problem is that the response rate is even lower than with the current checkpoint immune therapies. They’re really in the single digit efficacy. And the hard part of delivering the problem is of curing cancer via a cancer vaccine is that vaccine work very well, like for example, COVID or other disease that have been also eradicated by vaccines, right? But those worked because they were a preventative vaccine. They were administered before the disease could strike to prevent it. Now we’re talking about a vaccine that needs to target a disease that is already present. So the difference is that now there is a tolerance for these diseases or cancer. Our body is used to have these tumor cells growing, which as you know, takes decades to develop.

To break these tolerance, that is a central point of designing proper cancer vaccines. We are trying to figure out how extracellular vesicles may play a role in this tolerance induction and how we can revert those processes to break tolerance and have the ability to develop an effective therapeutic cancer vaccine that can work even if the disease is already present. This is the work that we have been funded to perform by the V Foundation.

How do you see immunotherapies shaping the future of cancer care?

A million dollar question. So I think the direction will be in simplifying the manufacturing, and so having therapies that are less expensive for both the healthcare system and the patients. So for example, off-the-shelf CAR T-cells or off-the-shelf NK cell therapies. The biologics will also play a huge role with the advance and the engineering of therapeutic antibodies and the development of biospecific antibodies and different conformation that can engage the immune cells with the tumor cells. Then there is the area of cancer vaccines. As we progress our understanding of how the immune system works and how we understand this complex biology and how the decision within the immune system are taken, who takes central decisions, who are the foot soldier that attack the tumor, we will get better to understand what is needed than to develop cancer vaccines. So this will be the furtherage of immunotherapy in the future, I believe.