Background Producing peptide-based cancer vaccines (pVACs) for use in clinical trials (CT) phase I/II in the European Union (EU) requires a GMP-certified facility, holding a valid manufacturing license. For smaller GMP facilities, the production of CT supplies has been increasingly difficult and costly due to recent changes in regulatory requirements in the EU. One approach to overcome these hurdles, to facilitate the fast-track translation of research findings into CT, is the close collaboration between the research and GMP departments. Thus, we have implemented a strategy for accelerated formulation design and production of pVACs.

Different therapeutic strategies can be addressed by using pVACs, comprising off-the-shelf single or multi agent vaccines (AML-VAC-XS15; NCT06252584), warehouse-based personalized vaccine composition (iVAC-XS15-CLL01; NCT04688385) and individualized de novo vaccine design (PerVision; NCT06094101). The latter represents the most complex, as peptide sequences for patient-specific pVACs will only be made available during the course of the study.

Methods In order to fulfill regulatory requirements for the different study designs a comprehensive and reliable vaccine production process has been implemented, utilizing thoroughly developed and validated manufacturing processes and analytical procedures. Our production capabilities include peptide synthesis comprising up to 22 amino acids followed by aseptic filling to gain vaccines containing up to 10 peptides. Peptides are manufactured by solid-phase synthesis employing Fmoc-chemistry under GMP conditions. Yields of the peptides are dependent upon their physiochemical properties, ranging from 50 mg to 200 mg. Prior to the production of GMP-peptides, feasibility and compatibility studies are necessary to investigate so far unknown peptides for production of personalized pVACs. These preliminary experiments are essential to ensure the compatibility of the final peptide vaccine formulation and trouble-free aseptic filling during GMP pVAC production. Peptides and pVACs are the subject of stability studies and are continuously monitored throughout the products life cycle. If a depot-effect is desired after vaccination, a mixing kit containing Montanide ISA™ 51 VG and the vaccine is supplied. Prior to application, the vaccine is emulsified with Montanide ISA™ 51 VG to protect the peptides from enzymatic elimination after vaccination.

Results To our knowledge we are the only GMP manufacturing facility for pVACs in Europe. This unique feature has allowed us to successfully supply pVACs to more than 210 patients in nine completed and seven ongoing clinical trials.

Conclusions In conclusion, the modular design for the fast-track production of pVACs has been successfully established to serve clinical vaccine trials to combat cancer.