Management and coordination is going according to plan: we organized a kick-off meeting, which took place on September 7, 2023 online. At the meeting, we officially presented the content of the project to the members of all PPs, the planned activities in the project by work groups, information on the coordination of the project implementation and the administrative obligations of the partnership, as well as the time frames for achieving the project results. At the meeting, a steering committee was also appointed, consisting of representatives of all participating PPs, which will take care of the flow of information within PPs, between individual PPs and between PPs and VPs. The first periodic meeting took place live on 26 January 2024 at the Celica premises in Ljubljana. An interview was also published in the local media: https://sis-egiz.eu/2024/01/30/preboji-so-na-pragu/. As part of the activities for the preparation of aHyC immunohybridomas, the partners ZTM, VBC and Celica determined the protocol for the preparation of nDC in the NANT-XL bioreactor and the specifications of the leukapheresis preparation for the isolation of monocytes. We prepared and adapted a protocol for the preparation of aHyC immunohybridomas for TNRD and prepared a clinical study protocol for the treatment of TNBC with aHyC immunohybridomas. 

On August 7, 2024, we held our second periodic meeting, focusing on key project milestones.
To ensure the regulatory adherence of our project, we proposed a collaborative workshop with national medicines agencies from Italy and Slovenia. This workshop aims to streamline the regulatory processes and foster cross-border cooperation. 
We synchronized the preparation and quality standards for the leukapheresis product in collaboration with ZTM. Additionally, we initiated the implementation of NANT technology within a Good Manufacturing Practice (GMP) environment in partnership with VBC. ZTM successfully optimized the apheresis procedure to produce the most suitable product for dendritic cell (DC) preparation. This involved fine-tuning the separation parameters. To validate the process, we conducted an apheresis collection from a healthy donor. During this validation, we measured several critical parameters, including platelet activation levels and the percentage of immunosuppressive monocytes (CD14+DR lo/neg) in peripheral blood before and after the collection, as well as in the final apheresis product. These measurements could serve as potential quality markers for future apheresis procedures.
We are now preparing to apply for a clinical trial to both the JAZMP (Agency for Medicinal Products and Medical Devices of Slovenia) and the National Ethics Commission. 
We have harmonized the preparation and quality standards for the product derived from leukapheresis. We have developed a protocol for nDC preparation in the NANT-XL bioreactor. We have prepared a protocol for the preparation of aHyC immunohybridomas for TNRD and a clinical study protocol for the treatment of TNBC with aHyC. 
To ensure the project's compliance with legislation, we conducted a workshop in November 2024 in cooperation with the Agency for Medicinal Products and Medical Devices of Slovenia (JAZMP). This workshop  was of great importance and yielded  significant outcomes, including the acquisition of information for finalization  of the legal and ethical requirements for including patients in a cross-border clinical study . The third periodic meeting of all partners was held online in February, 2025. At the meeting, all partners were informed on the project’s progress and agreed on further activities and a timeline. The protocol for the preparation of aHyC for the treatment of TNRD is ready to the extent currently feasible. Depending on the characteristics of the TNRD tumor cells, the protocol will be adjusted to match the characteristics and quantity of the TNBC tumor cells.
The GMP-compliant production of immunohybridomas for patients in clinical trial will be initiated immediately upon approval by the national authority, which is expected in the 4th period. We are implementing the NANT technology in a GMP environment. VBC installed NANT XL PLUS bioreactor at the Celica premises, performed a software upgrade and modified the protocol for DC isolation to increase the final yield. The synchronization of processes to increase the production of immunohybridomas with Nant technology in a GMP environment is ongoing. Five samples of leukapheresis have been obtained from ZTM and processed in parallel by manual method and by NANT-XLP bioreactor. The next step is to evaluate the results of differentiation success using the NANT bioreactor method compared to the manual method. After reviewing the clinical protocol by the National Ethics Committee and the National Medicines Agency (JAZMP), some issues were identified which are now being addressed in the revised protocol. In Italy, ASUFC and UNIUD identified suitable public and private hospitals and started with the recruitment phase.