Andrea Aroldi, MD, Hematology Division, San Gerardo Hospital, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy, overviews the CD24 ‘don’t eat me’ signal immune checkpoint blockade as a potential immunotherapeutic target for mantle cell lymphoma (MCL). These data were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

Transcript:

Dr Aroldi: Hello everybody. My name is Andrea Aroldi. I'm a physician-scientist and hematologist attending the Department of Medicine and Surgery at the University of Milano-Bicocca. I have an affiliation with the San Gerardo Hospital, Bone Marrow Transplant Unit, Hematology Department, where I am involved in the Bone Marrow Transplant Unit and the Immunotherapy Program in my institution.

I'm working both in clinic and in lab research, as well. I have experience that I gained abroad at Boston Children's Hospital in the Department of Pathology led by Dr (Roberto) Chiarle. I did work on CAR T-cells against solid cancer in childhood cancers, which is neuroblastoma. We developed a CAR T-cell against this type of solid cancer.

Then, I moved back in Italy to start by myself a immunotherapeutic project in blood malignancies. One of the projects involves the topic that has been discussed at ASH (American Society of Hematology Annual Meeting) last year in Atlanta.

Our group showed at ASH a study as pertains the potentiation of immunotherapeutic target on mantle cell lymphoma (MCL). We studied a new immune checkpoint blockade, which is called CD24. That is called also "don't eat me" signal.

We took a look at the previous analysis as pertains to the use of other immune checkpoint blockade involved in the so-called "don't eat me" signal. First of all, it was the CD47. That is the first "don't eat me" signal blockade that has been studied in Stanford University by Professor (Irving) Weissman (MD).

Recently, in 2019, there's a study published in Nature. First name, Dr (Amira) Barkal, which is a physician-scientist now working at Brigham Women's Hospital in Boston. She showed in this paper how CD24 can be considered a "don't eat me" signal in solid cancer.

She studied breast cancer, in particular, and she showed in vitro and in vivo, as well, how this target and this signaling involved can be associated with an improvement of phagocytosis, other than CD47, which means that there are new options to consider in case of "don't eat me" signal, and this study was the first one which demonstrate that CD24 can be used and considered as a "don't eat me" signal target.

Taking into account this study published in Nature 3 years ago, we tried to focus to study these pathway in a blood cancer. Since CD24 can be expressed in some phases of B-cell differentiation, and CD24 turns out to be over expressed in MCLs on the panel of cell lines available here in our main institution.

Our and my guess was to check if there's the possibility to improve phagocytosis once you inhibit this pathway when you co-culture macrophages and MCL in vitro.

What we found, and we shared those experiments at ASH last year, was effectively an improvement of phagocytosis when macrophages with a immunosuppressive phenotype, which is called M2-like phenotype, which is like an exhausted phenotype.

You found an improvement of phagocytosis when these macrophages are co-cultured with MCL lines with anti-CD24 monoclonal antibody, able to block the interaction between the ligand of CD24, which is Siglec-10, and the CD24 itself expressed on tumor cells.

The final results was an improvement of phagocytosis that we checked by flow cytometry.

Now we are moving forward with the other analysis at fluorescent microscopy which confirmed what we found at flow cytometry.

We are now moving forward to finalize, to conclude these preliminary results and to conclude this project. That's summed up what we are doing now here in Milano, Italy.