B Cell Engineering and Tertiary Lymphoid Structure Induction via Biomaterials for Cancer Immunotherapy

Introduction

Recent clinical evidence points to a potential new direction in immuno-oncology: utilizing B cells and B cell-associated tertiary lymphoid structures (TLS). B cells display diverse immunological actions, including antibody production, antigen presentation, cytokine secretion, and TLS induction.

Dual Role of B Cells

They have a dual role:

1. They can initiate and reinforce anti-cancer immunity.
2. B cells can also acquire regulatory phenotypes.

Objectives

To open up a new immunotherapeutic paradigm, I aim to understand how to optimally activate B cells, using nano-/biomaterials which load and precisely release a variety of agents to stimulate B cells and to suppress B cell regulatory phenotypes.

Scaffold Manufacturing

Furthermore, I will manufacture porous scaffolds based on injectable microgels or via 3D printing with microgel fibers to induce TLS formation.

Scaffold Features

The scaffolds with tunable porosity will allow:

• B cells and other immune/stromal cells to infiltrate, arrange, and expand.
• Soluble factors to diffuse.

Moreover, the scaffolds can be easily functionalized with different chemical cues to stimulate B cells for TLS formation, such as CXC-chemokine ligand 13 and interleukin-7. This will help us understand TLS induction.

Ex Vivo and In Vivo Studies

Importantly, I will use ex vivo engineered TLS to study what microenvironmental factors influence their functionality. Subsequently, in vivo formation of B cell-associated TLS will be induced by the scaffolds.

Combined Therapies

B cell activation and TLS induction will be combined for tumor therapy, and the potential abscopal effect of the treatment to address metastases will be studied. The materials will be further combined with checkpoint inhibitors and chemotherapy to reach synergism.

Patient-Derived Tumors

In addition, the new therapeutic strategies will be tested in patient-derived tumors established in humanized mice.

Conclusion

BeaT-IT aims to understand optimal B cell activation and TLS formation with nano-/biomaterials to establish a new direction in immuno-oncology, which is anticipated to realize an upcoming breakthrough in cancer immunotherapy.