Development of therapeutic monoclonal antibodies for the treatment of B cell non Hodgkin lymphomas – THERFL

Following the identification of a novel specific marker for B cell non-Hodgkin’s lymphomas, we have generated a specific antibody recognizing this marker. The aim is to characterize its mechanism of action and to assess its anti-tumoral activity in vitro and in vivo.

We have identified a novel marker that is specifically expressed by subtypes of B-cell non-Hodgkin’s lymphomas. We have generated a specific antibody and assessed its anti-tumoral activity. We are in the process of developing a humanized form of this antibody and we will measure its anti-tumoral activity in vitro and in vivo in preclinical studies. The ultimate aim is to provide a humanized antibody for clinical studies.

We hope to propose an alternative to current treatments, in particular to patients having developed resistance to treatments.

PCT/EP2001/060819

The aim of the project is the improvement of the treatment of cancer, in particular non-Hodgkin’s lymphomas (NHL), which are the sixth most common cancer of adults in France.
Targeted therapies are revolutionizing the paradigm of cancer treatment and are likely to be used in most cancer patients in the next 10 years.
Treatments of B cell NHL consist of immune-based therapies (anti-CD20 antibody, rituximab) combined with cytotoxic chemotherapies. Although they have significantly improved long-term survival, these therapies are not curative in the majority of B cell NHL patients and rituximab resistance has been observed. This necessitates to find alternative therapies and to develop novel agents that can overcome this resistance.
We have identified a novel target, LLT1 for Lectin-Like Transcript 1, which is upregulated by germinal center B cell –derived NHL such as Follicular lymphomas (FL), Burkitt lymphomas (BL) and some Diffuse Large B cell lymphomas (DLBCL) but not on Mucosa-associated Lymphoid Tissue lymphomas (MALT). Importantly, we have developed highly specific antibodies that show proofs of activity in vitro, acting by receptor blockade and having depleting properties. A patent protecting these antibodies is hold by the CNRS.
The aim of the scientific project is to consolidate the current studies to provide a proof of concept that LLT1 is a novel potent therapeutic target for the treatment of FL, BL and DLBCL patients and to provide 1st and 2nd generation anti-LLT1 mAbs with increased binding kinetics that show proofs of activity in vitro and in vivo. Importantly, our results will also provide a method to screen for fully humanized anti-LLT1 mAbs.
These data will be valuable to pharmaceutical companies interested in being granted the license of the patent and interested in developing treatments with these newly developed anti-LLT1 mAbs that could bring an added value to current treatments.