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Published on: March 20, 2026
In vivo targeting of B-cell lymphoma with glycan ligands of CD22
Weihsu C Chen1, Gladys C Completo, Darren S Sigal
1Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA.
Abstract:
Antibody-mediated cell depletion therapy has proven to provide significant clinical benefit in treatment of lymphomas and leukemias, driving the development of improved therapies with novel mechanisms of cell killing. A current clinical target for B-cell lymphoma is CD22, a B-cell-specific member of the sialic acid binding Ig-like lectin (siglec) family that recognizes alpha2-6-linked sialylated glycans as ligands. Here, we describe a novel approach for targeting B lymphoma cells with doxorubicin-loaded liposomal nanoparticles displaying high-affinity glycan ligands of CD22. The targeted liposomes are actively bound and endocytosed by CD22 on B cells, and significantly extend life in a xenograft model of human B-cell lymphoma. Moreover, they bind and kill malignant B cells from peripheral blood samples obtained from patients with hairy cell leukemia, marginal zone lymphoma, and chronic lymphocytic leukemia. The results demonstrate the potential for using a carbohydrate recognition-based approach for efficiently targeting B cells in vivo that can offer improved treatment options for patients with B-cell malignancies.
Insights
Researchers developed novel liposomal nanoparticles targeting CD22 on B cells for lymphoma treatment. These targeted nanoparticles effectively kill cancer cells and extend survival in preclinical models, offering new therapeutic options.
Area of Science:
- Oncology
- Nanotechnology
- Immunology
Background:
- Antibody-mediated therapies are effective for lymphomas and leukemias.
- CD22 is a B-cell specific target recognized by sialic acid binding Ig-like lectins (siglecs).
Purpose of the Study:
- To develop a novel targeted therapy for B-cell malignancies using CD22-ligand decorated liposomal nanoparticles.
- To evaluate the efficacy of these targeted nanoparticles in preclinical models of B-cell lymphoma.
Main Methods:
- Doxorubicin-loaded liposomal nanoparticles displaying high-affinity glycan ligands of CD22 were synthesized.
- Targeted liposomes were tested for binding and endocytosis by CD22-expressing B cells.
- Efficacy was assessed in a xenograft model of human B-cell lymphoma and in patient-derived leukemia cells.
Main Results:
- Targeted liposomes were actively bound and endocytosed by CD22 on B cells.
- Significant extension of survival was observed in a xenograft model of human B-cell lymphoma.
- Malignant B cells from patients with hairy cell leukemia, marginal zone lymphoma, and chronic lymphocytic leukemia were effectively bound and killed.
Conclusions:
- A carbohydrate recognition-based approach using targeted liposomal nanoparticles shows potential for efficient in vivo B-cell targeting.
- This novel strategy offers improved treatment options for patients with B-cell malignancies.
- The developed nanoparticles demonstrate promising therapeutic potential for B-cell lymphomas and leukemias.
