Four Questions with Mark Chao and Mauro Avanzi: Bringing Therapeutic Advances for Blood Cancers from Bench to Bedside

Stories@Gilead - December 03, 2020

Mark Chao and Mauro Avanzi have spent their careers working on the development of medicines that fight cancer by targeting a patient’s immune system. As the American Society of Hematology meeting, the world’s biggest – and this year virtual – gathering of the hematology community kicks off this week, the two scientists discuss advancements in immuno-oncology across Gilead and Kite.

This year Gilead and Kite have added significantly to the company’s oncology programs, through internal advancements, acquisitions and partnerships. Some of that work will be highlighted this week at ASH, as scientists share data from Kite’s chimeric antigen receptor (CAR) T-cell research and Gilead’s anti-CD47 program gained through the acquisition of Forty Seven earlier this year. In addition to the progress that the company is making in treating hematological cancers that will be showcased at ASH, Gilead took its first major step into the treatment of solid tumors with the recently completed acquisition of Immunomedics.

Mark, who is Vice President of Oncology Clinical Research at Gilead, and Mauro, who is Executive Director of Clinical Research at Kite, recently sat down with us to share their thoughts on the rapidly evolving field of immuno-oncology.

Q: Can you tell us about how you became physician-scientists and the experiences that helped shape your approaches to clinical development?
Mark: The early, meaningful experiences I had working with patients with leukemia in medical school taught me how to understand translational data so that I could ask the right questions in the lab. Hematology is a field where the science is often quickly implemented in the clinic soon after we gain insights in the lab. I was fortunate to work on early preclinical studies that showed incredible promise and brought that knowledge into a clinical setting. I like to say that it comes down to determination, and ultimately, some luck.

Mauro: I agree with Mark. There’s always an element of trial and error, especially with novel therapies. I started working on stem cell research when I first moved to the United States from Brazil and eventually transitioned to CAR T-cell research before joining Kite. While in academia, we needed to figure out the types of blood cancers that could be the right candidates for CAR T cells to target. With technologies that are new, nobody has those answers – you need to find them yourself. When you find something that seems promising, you start to explore it in different types of cancers. With CAR T, the scientific rigor paid off. What we first thought might work, didn’t. If we had stopped then, we wouldn’t have advanced to the stage we are at now. Working with CAR T-cells in the laboratory for many years and now at Kite being able to witness firsthand the benefits that this type of therapy brings to patients is quite an experience.

Q: What is your research focused on now?
Mauro: We’re expanding CAR T into different types of blood cancers and earlier lines of therapy. And most importantly, we are finding ways for the therapy to be delivered to more people who may benefit. We’re also starting to see data that would have been hard to imagine when we first started.

Mark: My team and I focus our research on harnessing the power of macrophages, cells that are the “first responders” of the immune system. Some researchers have linked macrophages to tumor growth and evasion, but we saw the potential of these cells to target cancer instead. One of the investigational therapies we are developing has demonstrated the potential to block the CD47 receptor, a protein that is thought to send a signal that allows cancer to escape elimination by the body’s immune system. Targeting CD47 has the potential to block that signal, allowing the immune system’s first responders to do their job. I’ve been involved in this program since preclinical studies and it’s encouraging to see the field now starting to recognize the unique role of macrophages.

Q: What advances in the immuno-oncology field are you working to explore next?
Mark: There have been dramatic advances in addressing blood cancers since the early 2000s – but there is still much to be done. With a disease such as acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), there have been few approved therapies in the last decade, so it’s really motivating to work in this space. Based on early results, we’re moving our investigational anti-CD47 therapy into Phase 3 studies for both MDS and AML, which is especially challenging to treat and has a poor prognosis.

Mauro: Ten years ago, CAR T-cell therapy research was still in its very early stages of development. Now, we’re seeing research data demonstrating promising results even four years after treatment and showing potential beyond the very sickest patients. I am looking forward to the forthcoming data that Kite will be releasing at ASH.

Q: As leaders in clinical research, where is the immuno-oncology field headed?
Mauro: I’m excited to see just how much CAR T therapy can help advance cancer care. CAR T has demonstrated its success in practice, and more importantly, in long-term follow-up. Now research is moving into investigating CAR T as an earlier treatment option and in combination with other agents, so I’m excited to see even more significant advancements.

Mark: I’m looking forward to seeing how far we can push the transformation of cancer treatment. So much has changed in the last 10 years – we’re now even seeing promising research suggesting that certain blood cancers with limited treatment options may one day become chronic diseases that can be managed. This progress is incredibly encouraging and inspires us to keep going.