Immunotherapy against ovarian cancer

The Fraunhofer-Institute for Cell Therapy and Immunology IZI supports the Australian biotechnology company Prima BioMed Ltd. in testing and licensing of new treatments for ovarian cancer. The cell-based, autologous immune therapeutic agent (medication for novel therapies – ATMP) will be tested for efficacy and safety in a clinical trial to obtain authorization for its clinical use in Europe.

The Fraunhofer IZI is developing the process transfer, is establishing quality standards according to GMP, and is validating all methods within the process chain. The investigational drugs will be prepared in clean rooms of the Fraunhofer IZI, their quality will be tested, and finally they will be released for use.

Ovarian carcinoma is one of the most common cancers in women.
The malignant disease is treated by operative removal of the tumor with subsequent chemotherapy. Both treatments are a great burden for the patient. Aside from the stage in which the disease was diagnosed, the amount of remaining cells after the operation is especially important for the prognosis.

It is usually poor despite treatment, because the disease is frequently diagnosed in an advanced stage. A new immune therapeutic method that is used in addition to the abovementioned standard therapies will improve the survival rate.

The Australian company Prima BioMed Ltd. is developing an autologous (body’s own) immunotherapy for the treatment of epithelial ovarian cancer. Together with the Fraunhofer-Institute for Cell Therapy and Immunology IZI efficacy and safety of the new method will be tested in a clinical study and the way will be paved for European marketing approval.

The autologous immunotherapy CvacTM is based on the modification of the body’s own immune cells. Tumors escape the immune defense by various mechanisms, because they develop from degenerated body cells. The immune system does not identify tumor cells as foreign or degenerated and tolerates their growth.

The CvacTM-method modifies specialized patients’ immune cells so that these can activate different tumor-specific defense mechanisms. These so-called dendritic cells are imprinted for a certain protein (biomarker) that is mainly found on tumor cells in a specially modified form, but not on healthy body cells. After such a treatment, the immune system is capable of specifically attacking tumor cells without affecting healthy cells. Therefore, this therapy is a useful supplement to standard therapy (usually chemotherapy). It promises a reduction of the relapse rates.

Initially the task of the Fraunhofer IZI was the process transfer. For this purpose, together with the client in Leipzig, the production method for the cell-based immune therapeutic agent including the necessary quality controls was established, successively developed further, and adjusted to the European legal standards. The production process as well as the approval relevant quality controls were validated according to current laws and guidelines (e.g. according to annex 15 of the EU-GMP-Guideline, the European Pharmacopoeia, and ICH Guideline Q2A/2B).

The validation of the analytical methods involved in particular flow cytometry, as well as tests for sterility, bacterial endotoxins, and mycoplasma. In addition, the qualification of the clinical partners was necessary to ensure quality high-grade isolation of the cellular source material. Subsequently, this is processed to CvacTM exclusively in clean rooms of the Fraunhofer IZI under sterile conditions.

The production license according to §13 Drug Law (Arzneimittelgesetz) has already been obtained at the responsible pharmaceutical authority (state department together with the Paul-Ehrlich-Institute) based on this validation. With the approval of the authorities, the requirements have been met to make the cell-based clinical investigational drugs for clinical trials available.

The joint project is funded by the Sächsische Aufbaubank with 4.1 million Euros from the European Fund for Regional Development (EFRE).