The problem: Poor clinical outcome of patients with aggressive B-cell lymphoma after immunotherapy. Immunotherapy using antibodies targeting the cell surface has led to important clinical advances in patients with cancer, exemplified by CD20-antibodies that are first-line treatment in patients with B-cell lymphoma.1 However, diffuse large B-cell lymphoma (DLBCL), the most common and aggressive form of B-cell lymphoma worldwide, is still incurable in approximately 40% of patients. These patients have poor prognosis due to treatment failure or relapse upon therapy with CD20-antibodies (260,000 mortalities worldwide in 2020). Thus, there is urgent need for novel therapies to overcome resistance and enhance anti-tumor activities in patients with aggressive B-cell lymphoma.
The solution: A more effective immunotherapy that uses nanofilaments to induce potent lymphoma cytotoxicity by clustering membrane targets and dual targeting. We developed nanofilaments that can efficiently cluster multiple lymphoma membrane targets to induce potent tumor cytotoxicity. This represents a powerful strategy since this approach is independent from genetic cancer subtypes and is broadly applicable in molecular heterogeneous B-cell lymphoma subtypes. Development of this novel technology for clinical use will result in:
1. Improved tumor cytotoxicity, as clustering of targets will increase complement-dependent cytotoxicity and direct apoptotic signaling.
2. Prevent resistance by dual targeting of two membrane targets at the same time.
3. Broadly applicable treatment approach, as targeting of membrane proteins is independent from genetic heterogeneity among lymphoma subtypes.
