Source: www.targetedonc.com
Author: Sabrina Serani

In an interview with Targeted Oncology, Mark Dybul, MD, discussed a breakthrough method of immunotherapy in solid tumors.

Mark Dybul, MD

Treatments for difficult-to-treat tumors like pancreatic cancer and triple-negative breast cancer are lacking in availability and efficacy. However, Mark Dybul, MD, identified that a key to treating these cancers lies in retraining a patient’s immune system.

Unlike some approaches using exogenous immunomodulators, this method focuses on the patient’s immune system. The dendritic cells are genetically modified from another person, enhancing immune stimulation. The combination of allergenic cells from another person, genetically modified dendritic cells, and tumor pieces aims to retrain the immune system to recognize and combat cancer differently. Preliminary data show promising results.

In an interview with Targeted OncologyTM, Dybul, chief executive officer of Renovaro Biosciences, professor in the Department of Medicine at Georgetown University, and senior advisor at the Center for Global Health Practice and Impact, discussed how Renovaro’s breakthrough immunotherapy works and how it differs from currently available therapies.

Targeted Oncology: What are some of the new immunotherapy technologies on the horizon?
Dybul: The immunotherapies are, in our view, incredibly promising and exciting. [Renovaro’s] mission is to create a future free from toxic chemotherapy by retraining the immune system to recognize and control or eliminate a possible cancer and to have an ongoing ability to surveil and prevent recurrence. We believe it is very possible, and our preliminary data suggest that is the case.

Our approach is to, again, retrain the person’s own immune system, not by exogenous [means] or bringing in immunomodulators that some people are working on, but to use the [patient’s] own immune system to stimulate it in a new way. We stimulate the immune system by using the orchestrator of the immune system, what’s called the dendritic cell.

There’s a lot about the immune system we do not understand or know about. If you look at what we thought of the immune system 20 years ago, when we think of it today, it’s radically different. When I was in [Anthony Fauci, MD, former director of the National Institute of Allergy and Infectious Diseases] lab 30 years ago, working on dendritic cells with Drew Weissman [MD, PhD, Roberts Family professor in vaccine research at the University of Pennsylvania Medicine], who just received the [2023 Nobel Prize in Physiology or Medicine] for the mRNA vaccine, we understood something of the immune system. But we know muchmore about it now.

While we are excited about certain therapies like [chimeric antigen receptor T-cell therapy] or natural killer cells or picking an enemy modulator or certain pieces of tumors that could stimulate the immune system, we know that the immune system is much more complicated than we think. We know that cancer will adapt to whatever it is challenged by, and we know this is why we have people fail chemotherapy.

Rather than trying to outsmart that, we use the dendritic cell, and then we genetically regulated for pieces we do know hyper-stimulate the immune system. We use those dendritic cells that are genetically modified from another person, which is the biggest immune stimulant. The whole body is trained to recognize things that do not belong there. This combination of what is called allergenicity cells from another person genetically modified the dendritic cell, then putting a piece of the tumor onto the dendritic cell, rather than guessing what the dendritic cell would use of the tumor. By using that combination, we believe we can retrain the immune system to see the cancer in a different way, because cancer occurs because of a failure of the immune system.

The results have been, in our view, spectacular. [Anna Jewett, PhD, MPH, professor and director of the Tumor Immunology Laboratory at the University of California, Los Angeles] just named by Stanford University as among the top 2% of scientists in the world, has conducted all our pivotal trials and in laboratory and in humanized mice, which imitates the human immune system. She says our results are what she calls the holy grail of cancer research. That’s because of that hyper-stimulation that re-presenting of the cancer to the immune system and lets the immune system dictate how to respond.

What cancers is this type of immunotherapy best suited toward?
Solid tumors are 80% of all cancers, so that is one of the reasons we focus on solid tumors. Also, the nature of liquid tumors or blood type tumors is a little bit different. We are targeting solid tumors to begin with. The 2 we are starting with [are] pancreatic cancer and other solid tumors that are difficult to treat. For example, triple-negative breast cancer, head and neck, parts of prostate cancer with certain genetic variations.

There are few cancers that we have poor therapy for and therefore, a poor life expectancy. From a humanitarian perspective, we would like to engage in tumors that are difficult to treat, where people really have little hope. An example in pancreatic cancer: In the United States alone, 60,000 people [are] diagnosed every year [and there are] 40,000 deaths. Triple-negative breast is similar.

From a regulatory perspective, if you are focused on tumors that are difficult to treat, you can move much faster through the regulatory system. In fact, we’ve seen recently with FDA approval for biologics…with dozens of patients vs the hundreds that you need in other types of cancers. Also, in cancers with good first-line therapy, you have to wait until people have failed the first- or second- or third-line therapy before you can be begin to intervene. By then, it is difficult to intervene because the immune system is compromised in a significant way. However, I would point out that if you can effectively treat difficult-to-treat cancers, you should be able to treat easy-to-treat cancers.

What are some of the safety considerations?
One of the beauties of this therapy is we do not see the risk of a great deal of toxicity. We are not seeing it all in the animal models. The reason for that is the allergenic cells we use, because they are dendritic cells, we do not need large numbers. We are talking about millions vs the billions, trillions that you need in bone marrow transplants. It really is, effectively, a vaccination approach. This would be an intermuscular [infusion] of a relatively small number of cells that the person’s own immune system would remove because they are allergenic. But at the same time, it would stimulate an immune response that is new, because it is seeing the cancer in a new way, coming off a cell from another person that is already designed to stimulate a broad immune response with the cancer on it.