Tb535 is a T-cell engager Tribody™, against a validated target found in various subtypes of Malignant Mesothelioma. Tb535 targets the tumour cells and engages T-cells to induce cell killing via an anti-CD3 effector function.
Malignant Mesothelioma (MM) is a highly heterogeneous and highly aggressive cancer of serosal surfaces, such as the pleura and the peritoneum. It is almost always caused by sustained exposure to asbestos, but has minimal association with smoking.
According to the WHO classification, malignant mesothelioma is sub-classified as either: epithelioid (mostly composed of epithelial-shaped cells); sarcomatoid (mostly composed of spindle-shaped cells); or biphasic (composed of both types of cell). Several studies reported the association between malignant mesothelioma subtype and patient prognosis. Indeed, a purely epithelioid histology involved the longest survival, a purely sarcomatoid histology the worst, and a biphasic pattern an intermediate survival (depending on the ratio epithelioid/sarcomatoid).
In a large series of malignant mesotheliomas, there was a consistent epithelial-to-mesenchymal trend in marker representation coinciding with the epithelioid to biphasic, to sarcomatoid histotypes. Contrary to previous believe that the different forms initiate from different tissues, the morphological patterns of malignant mesothelioma are now thought to be a result of different steps in an epithelial–mesenchymal transition process. This insight puts more weight on targeting the less frequently diagnosed but far more aggressive and therapy-resistant sarcomatoid form.
A potentially successful drug candidate should be able to show efficacy against the various subtypes.
Biotecnol has validated and shown a very high efficacy of Tb535 in various subtypes of this highly heterogeneous cancer and is further developing Tb535 as a first-in-class product for treating such a lethal disease.