This presentation is part of CLL Global Research Foundation’s first-ever Patient-Focused research symposium, featuring CLL Global–funded researchers sharing insights from their latest studies and clinical trials—showcasing how their work is directly improving outcomes for patients with chronic lymphocytic leukemia (CLL).
Expert Presenter:
Maria Teresa Sabrina Bertilaccio, PhD
Assistant Professor, Department of Leukemia
The University of Texas MD Anderson Cancer Center
Download the slide deck.
Transcript:
Dr. MT Sabrina Bertilaccio: Good afternoon, everyone. I would like to thank CLL Global Foundation for the opportunity to present our research. My work is dedicated to all patients with leukemia who are fighting this disease every day. Patients and their families truly inspire this research.
Chronic lymphocytic leukemia cells are not alone on isolated islands in our body. But they are constantly surrounded by non-cancerous cells of the immune system that are all described here in this slide. Actually, initially, during leukemia development, some of these immune cells, non-malignant cells, try to fight leukemia through a physiological process that is called tumor immune surveillance. But during, unfortunately, during leukemia progression, this natural process of immune surveillance is sabbated. These immune cells do not work anymore. They do not recognize leukemia as the enemy anymore.
Additionally, some new immune cells with pro-tumor function appear during leukemia progression, and actually, they help, they grow in number, and they help leukemia growing. So, CLL as tumors in general are driven by an imbalanced immune system. We have in the body some immune cells that immediately help us to fight infection and also help to initiate what we call the memory immunity that protects us against infection even a long time after we encounter a pathogen. But some of these immune cells, unfortunately, have also an important role during CLL and cancer development. As you can observe here, they can have an anti-tumor or pro-tumor role. And actually, the goal of my team is to re-educate some of these immune cells against leukemia to re-establish our physiological and natural immune surveillance.
To re-educate the immune system to combat leukemia, we are actually exploiting a number of immune-therapeutic strategies, and here, I listed two of this strategy we evaluated in CLL. The first one is more of pharmacological approach that involved the use of what we call immunomodulatory drugs. The second one is a self-therapy approach that is based on the engineering in the lab of some immune cells to make them live in drugs. One of the immunomodulatory drugs we actually evaluated in CLL is called trabectedin (Yondelis).
And actually, when we tested this drug on cells from the peripheral blood donated from some patients with CLL, we observed two important, at the same time, two mechanisms of action of this drug. This drug was able at the same time to kill some bad cells of the immune system, the one with the red cross here in this cartoon that normally help leukemia growing. But at the same time, this drug was able to arm some good immune cells with this colored dot, you can see in the cartoon, that are killer bullets with the common goal of all these cells to kill leukemia altogether.
There are cells in our immune system that are known as the lymphocytes that can be engineered in the lab and actually decorated with some molecules we call kinetic antigen receptors to precisely kill leukemic cells. Precisely target and kill leukemic cells. So, we engineered to emphasize from the peripheral blood the patients with CLL with what we call CD23 kinetic antigen receptor. We also combine these engineered T cells with lenalidomide (Revlimid), another immunomodulatory drug that is very well-known, having a powerful effect on the immune system. When we combine these engineered T cells with lenalidomide, actually, we observed that this drug was able to increase the killing capacity of engineered T cells, but also to educate other immune cells of our body to starve the remaining leukemic cells.
I hope I have convinced you that our own immune system hides a high variety of tools that can be exploited to kill leukemic cells and cancer by themselves. But we need to better study and understand these immune cells to exploit them in their full capability to kill cancer. What we are doing now, is to try to understand the genetic code of some immune cells with the aim to re-write this code for therapeutic purposes. We recently started another cell type very interesting immune cell, they are called monocytes, and what we discovered is that when these monocytes get in contact with leukemic cells, actually, they are able to modulate small pieces of their RNA which are called micro-RNA. And if we manipulate in the lab these small pieces of RNA, we can actually transform these monocytes and make them anti-tumor.
So, I truly believe that based on this new knowledge, we can build a new class of living drug not only to kill leukemia, but all cancer in general. To conclude, I would like to thank immensely all patients with CLL and their families. My wonderful team member and collaborators, the CLL Global Foundation, all our funding agency and our donors for making all these studies and discoveries possible every day.