# Finding the Sweet Spot for the Treatment of B Cell Malignancies

## TL;DR

This paper reviews how sugar decorations on B cell cancers differ from healthy cells and explores ways to target these sugars for cancer treatment.

## Contribution

The paper highlights novel therapeutic strategies targeting aberrant glycans in B cell malignancies, including lectin-based therapies and glycan-modulated immunotherapy.

## Key findings

- Aberrant glycans like high mannose N-glycans and Gb3/CD77 are present in B cell malignancies and can be targeted for therapy.
- Glycan profiling reveals opportunities for lectin-based and drug-conjugate therapies in treating B cell cancers.
- Modulating glycans can enhance immunotherapy, including CAR T cell therapy, for B cell malignancies.

## Abstract

Most proteins and lipids in our cells are ‘decorated with sugars’. These sugar decorations commonly differ between cancer cells and healthy cells and are therefore of interest for therapeutic targeting. This review is focusing on sugar decorations that are present on B cell malignancies, including both B cell leukemia and lymphoma. Furthermore, potential ways to target these sugar decorations for the treatment of B cell malignancies are discussed. The final section describes the hurdles that still need to be taken before therapies that focus on the sugar decorations of B cell malignancies can be translated to the clinic.

The glycan profile of cells comprises a high variety of sugar moieties that are attached to proteins (glycoproteins) and lipids (glycolipids) via a process called ‘glycosylation’. Cancer cells commonly carry aberrant glycans, which may be of interest for cancer diagnosis, prognosis, as well as the development of novel therapeutic strategies. This review focuses on the differential glycosylation patterns on malignant B cells, including both B cell lymphoma and leukemia. Well-known aberrant glycan profiles on malignant B cells include acquired high mannose N-glycans in the B cell receptor (BCR) of follicular lymphoma (FL), and increased expression of the glycosphingolipid Gb3/CD77 on Burkitt’s lymphoma (BL). These structures can be exploited for therapy by using lectins that specifically recognize these patterns with intrinsic cytotoxic activity or in a drug-conjugate format. Furthermore, immunotherapy can be improved by modulating glycans, especially sialic acids. Targeting glycans for immunotherapy is also of interest for chimeric antigen receptor (CAR) T cell therapy, a relatively novel therapy that has been quite effective in various B cell malignancies. Thus, the glycan profile of malignant B cells harbors many opportunities for therapeutic targeting. It is anticipated that further in-depth glycan profiling will open up many more opportunities for the treatment of B cell malignancies.