Curing ovarian cancer through autoantibody-based therapy

Descripción del proyecto

Avances en el tratamiento con anticuerpos del cáncer de ovario

Los conjugados anticuerpo-fármaco (CAF) son una clase de medicamentos biofarmacéuticos diseñados para el tratamiento dirigido del cáncer, que consisten en un anticuerpo monoclonal conjugado con un agente quimioterapéutico. A pesar de sus prometedoras ventajas, como el aumento de la especificidad y la reducción de la toxicidad sistémica, los CAF están limitados por la identificación de antígenos tumorales adecuados. El equipo del proyecto OVCure, financiado por el Consejo Europeo de Investigación, se centra en el cáncer de ovario y en un CAF dirigido a MUC16, el mejor marcador diagnóstico de la enfermedad. El equipo ha identificado un anticuerpo dirigido a un epítopo antigénico MUC16 en la superficie del tumor. En el estudio se pretende optimizar la composición y validar la eficacia de este CAF para el tratamiento del cáncer de ovario en modelos preclínicos.

Objetivo

Ovarian cancer (OC) is a malignant tumor with poor prognosis and limited treatment options, responsible for 4.4% of cancer-related mortality in women. There is an urgent need for innovative therapeutic approaches for OC. Antibody drug conjugates (ADCs) represent one of the most promising therapeutic approaches, but their efficacy has been hindered by identification of suitable tumor-associated antigens. For example, ADCs targeting MUC16, the best diagnostic marker for OC, have thus far failed in clinical trials due to shedding of MUC16 from the tumor. Our breakthrough lies in the identification and characterization of a MUC16-specific autoantibody clone 2B5, which specifically targets the non-shed and highly conserved epitope of MUC16 that stays associated with the tumor. This consequently, dramatically increases the efficacy of the cytotoxic payload delivery to the tumor, and overcomes limitations of similar ADCs that have failed in the past. By directly and selectively targeting MUC16 on OC, while sparing healthy tissues, our ADC has the potential to revolutionize OC therapy by finally offering a precise and effective ADC cancer treatment. Thus, for this PoC, we aim to demonstrate the effectivity of our 2B5-based ADC, as a leading candidate for OC therapy in humans. In order to increase its therapeutic and commercial potential, the 2B5-based ADC will be developed further to identify the most suitable payload, as well as to validate its tumor killing efficacy in pre-clinical animal models, which will be developed in frame of this project. By the end of this PoC, we aim to be ready to develop our 2B5-ADC to human grade towards phase 1 clinical trials. Simultaneously, we will define the innovation commercial feasibility and business model and will validate the business opportunities and go-to-market strategies with relevant stakeholders. Furthermore, we have already initiated the process of patenting our innovation and aim to finalize it during the PoC.