Periodic Reporting for period 1 - MACOV (Macrophage-based immunotherapy of platinum-resistant ovarian cancer)
Período documentado: 2022-11-01 hasta 2023-10-31
Resistance to platinum-based chemotherapy is a major clinical challenge in ovarian cancer. About 300,000 women are diagnosed
with ovarian cancer each year and the number of deaths is estimated at 180,000 worldwide each year. Ovarian cancer metastasizes
early in its development, often before it's diagnosed. Ovarian cancer treatment involves surgery with frontline platinum-based
chemotherapy. As many as 15-30% of patients with ovarian cancer have primary platinum-resistant or refractory disease. The
recurrence of ovarian cancer is now considered a sign of an incurable disease (it becomes platinum-resistant).
The project MACOV aims to develop an innovative allogeneic, “ready-to-use” macrophage-based therapy for platinum-resistant
ovarian cancer. This is a ground-breaking, first in class therapy that shows very high efficacy in multiple solid tumors of unmet medical
need.
These cells are equipped with targeted therapy drugs complexed with the carrier protein ensuring their stability in the carrier cell. The
protein-drug complex is transferred specifically to cancer cells. The whole concept of this cell therapy is based on the groundbreaking
scientific discoveries of MDC (Macrophage-Drug Conjugate). Two European Research Council (ERC) grants were received to study the
molecular basis of the discovered mechanism - in 2016 and 2020. In 2018 this project was selected to be promoted as one of the 10
European projects during ERC 10th Anniversary.
The MACOV project will generate of complete efficacy data package for the pre-clinical development of MDC-735 product, consisting
of efficacy in multiple animal models for platinum-resistant ovarian cancer, PK, PD and toxicology study as well as consolidate IP and
validate business case. The result of the project will be a validated cell therapy product for platinum-refractory ovarian cancer, tested
for effectiveness and ready-to-use for the Phase I clinical trial.
with ovarian cancer each year and the number of deaths is estimated at 180,000 worldwide each year. Ovarian cancer metastasizes
early in its development, often before it's diagnosed. Ovarian cancer treatment involves surgery with frontline platinum-based
chemotherapy. As many as 15-30% of patients with ovarian cancer have primary platinum-resistant or refractory disease. The
recurrence of ovarian cancer is now considered a sign of an incurable disease (it becomes platinum-resistant).
The project MACOV aims to develop an innovative allogeneic, “ready-to-use” macrophage-based therapy for platinum-resistant
ovarian cancer. This is a ground-breaking, first in class therapy that shows very high efficacy in multiple solid tumors of unmet medical
need.
These cells are equipped with targeted therapy drugs complexed with the carrier protein ensuring their stability in the carrier cell. The
protein-drug complex is transferred specifically to cancer cells. The whole concept of this cell therapy is based on the groundbreaking
scientific discoveries of MDC (Macrophage-Drug Conjugate). Two European Research Council (ERC) grants were received to study the
molecular basis of the discovered mechanism - in 2016 and 2020. In 2018 this project was selected to be promoted as one of the 10
European projects during ERC 10th Anniversary.
The MACOV project will generate of complete efficacy data package for the pre-clinical development of MDC-735 product, consisting
of efficacy in multiple animal models for platinum-resistant ovarian cancer, PK, PD and toxicology study as well as consolidate IP and
validate business case. The result of the project will be a validated cell therapy product for platinum-refractory ovarian cancer, tested
for effectiveness and ready-to-use for the Phase I clinical trial.
In WP2 (milestone number 1) we successfully implemented the cell killing assay into MACOV project. The results from in vitro experiments showed that platinum-sensitive and platinum-resistant ovarian cancer cells are sensitive to MDC-735 treatment. In WP2 (milestone number 2) we investigated MDC-735 therapy in mice implanted with platinum-sensitive and platinum-resistant ovarian cancer cells. In both groups we observed a significant increase in tumor-bearing mice survival after treatment with MDC-735. Currently, we are performing biodistribution study of the 735 drug in various organs of tumor-bearing mice to choose the best treatment regimen in therapeutic window study and seeking subcontractors to test MDC-735 in patient-derived xenograft (PDX) platinum- resistant ovarian cancer model. So far, the Macov Project implementation is progressing as planned.
The in vivo animal studies showed that MDC-735 was able to cure half of the platinum-resistant ovarian cancer - bearing animals. This is exceptional achievement in the field.