Early Research on Targeting the Sugar Coat of Tumors Cells Expands to Hematologic Malignancies

Robert Sackstein, MD

Among the many evolving therapies in the oncology space, there is novel strategy of targeting sugars on the surface of cells (glycans), as a way to reduce or stop tumor growth. Targeting the “sugar coat” of cells is the next important thing in immunotherapy for cancer, according to Robert Sackstein, MD.

Experts at the Herbert Werthein College of Medicine at Florida International University (FIU) know that glycans have the ability to drive the development of cancer by causing tumors to grow. The experts have begun to further investigate the theories around sugar coating to better understand the role of sugars in cancer development and potentially pave the way for new treatments. Previous research around targeting the sugar coat led to the creation of an antibody that targets glycans on ovarian cancer cells.¹

Recently, Sackstein, a bone marrow transplant physician and biomedical researcher at FIU, discussed targeting the sugar coat in hematologic cancer cells during the Summit of the Americas on Immunotherapies for Hematologic Malignancies.

“We wanted to cover the different cancers that cover the entire body so that we can understand how glycans displayed on cells within the various tissues fuel the development of cancer and control the ability of cancer to metastasize, said Sackstein, in a statement.

In an interview with Targeted Oncology™, Sackstein discussed ongoing research around use of the sugar coat method to potentially aid in cancer treatment, and particularly in hematologic malignancies.

TARGETED ONCOLOGY: What is the latest area of excitement related to immunotherapy in hematologic malignancies?

Sackstein: One of the reasons I recently took the opportunity to present during the Miami Cancer Institute Summit of the Americas on Immunotherapies for Hematologic Malignancies is to discuss the important role that sugar modifications on the cell surface may play in defining different types of malignant cells in the body. This works by taking that approach of looking at the cell surface sugar composition to identify new determinants for immunotherapy and being able to target those kinds of cancer cells.

Can you explain how sugar modification works?

There are 4 major macromolecules in all of biology. There are your proteins, your lipids, nucleic acids, and then you've got your sugars. Now, if you look at the biomass of the planet, the overwhelmingly largest macromolecule in terms of content, and breadth and scope, are the sugars, it's the glycans. As you look around anywhere in a room that you might be sitting in, all of the wood in front of you is a carbohydrate, that's a sugar, that's cellulose. And yet, we don't appreciate the fact that sugars control a lot of processes biologically, on the surface of cells.

During my presentation, I brought to the attention of my colleagues, how we can exploit the fact that every cell has a sugar coat, that's unique, that will give us an opportunity to target cancer cells. So just like a cancer cell is a rogue cell that has unique proliferative capacities that can it grow and propagate faster than normal cells will. In the process of becoming rogue, it also changes its sugar coat, and we want to find a way to find the specificity of those changes in the sugar coat on a cancer cell and allow us to target immunotherapy against that kind of structure.

Why should community oncologist know about this novel immunotherapy strategy?

I think this is the future of immunotherapy. This concept is evolving and there are numerous clinical trials now ongoing where we're using anti-carbohydrate-based immunotherapeutic approaches. As 1 example, the antigen that we call CA19-9 is a carbohydrate. There are clinical trials using antibody approaches as well as CAR T- and NK cell approaches against CA19-9.

Another molecule, which people may just use is GD2, which is a glycosphingolipid. It's a carbohydrate modification on a lipid. And that is also getting a lot of clinical trial attention.

Are any of these methods showing success?

Anti-GD2 to therapeutics are really mainstream now in central nervous system tumors like neuroblastoma, and things of that nature, and it’s being tested heavily now in gliomas. So, that's a clear path forward. There's a variety of different therapeutic approaches now for ovarian cancer, which are looking at carbohydrate specifics, and changes on ovarian cancer cells. So, I think that over the next year, and year and a half, we're going to see rollout of true clinical entities directed to this class of molecules. And then everyone will want to learn a little bit more about this, which is otherwise not mainstream.

_REFERENCE:

_{Targeting the sugar coating of cancer cells: FIU takes lead in cancer research. New release. Florida International University. September 22, 2021. Accessed May 5, 2022. https://bit.ly/3P0ICsx}