Periodic Reporting for period 1 - NanoLymphoma (Novel therapeutic platform for aggressive lymphoma: NanoLymphoma)
Periodo di rendicontazione: 2023-09-01 al 2025-02-28
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.
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.
We developed a novel therapeutic platform for cancer that differs from conventional immunotherapies by its multivalent and dual targeting approach and its broad applicability to different cancer types. Specifically, we generated dual-targeting nanofilaments containing multiple tumor-targeting antibodies to increase avidity, clustering and tumor cytotoxicity. Membrane target clustering will enhance cell death signaling into tumor cells. As such, these new nanofilaments are expected to outperform conventional anti-CD20 (rituximab) treatment in patients with B-cell lymphoma. The current technology readiness level is TRL3 we investigated the applicability of the concept in in vitro cell-based models. Our proof-of-concept data show that tumor-targeting nanofilaments are more potent in mediating direct tumor killing than soluble therapeutic antibodies (standard-of-care) in different human lymphoma cell models.
A patent application has been filed (February 2025). To define the optimal path for commercialization of NanoLymphoma, an extensive market and competitor analysis of antibody-based treatments for aggressive lymphoma will be performed. The market and competitor analysis will focus on the following aspects: 1) research on market entry into DLBCL and later followed by other (haematological) cancers, 2) price-driving factors, 3) prices of current competing technologies competitors and their limitations, and 4) identification of potential customer bases. This way, key threats in the market and opportunities for collaboration will be identified, thus providing a strong basis to define the business strategy.