% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Wohlfarth:177493,
      author       = {D. Wohlfarth$^*$ and V. Frehtman$^*$ and M. Müller$^*$ and
                      M. Vogel$^*$ and L. M. P. Phan$^*$ and A. Brunecker$^*$ and
                      B. Leuchs$^*$},
      title        = {{U}pstream process optimization and micro- and macrocarrier
                      screening for large-scale production of the oncolytic {H}-1
                      protoparvovirus.},
      journal      = {Applied microbiology and biotechnology},
      volume       = {105},
      number       = {24},
      issn         = {1432-0614},
      address      = {New York},
      publisher    = {Springer},
      reportid     = {DKFZ-2021-02580},
      pages        = {9113-9124},
      year         = {2021},
      note         = {#EA:F010#LA:F010# / 2021 Dec;105(24):9113-9124},
      abstract     = {The oncolytic virus H-1PV is a promising candidate for
                      various cancer treatments. Therefore, production process
                      needs to be optimized and scaled up for future market
                      release. Currently, the virus is produced with minimum
                      essential medium in 10-layer CellSTACK® chambers with
                      limited scalability, requiring a minimum seeding density of
                      7.9E3 cells/cm2. Production also requires a $5\%$ fetal
                      bovine serum (FBS) supplementation and has a virus yield up
                      to 3.1E7 plaque-forming units (PFU)/cm2. Using the
                      animal-free cell culture medium VP-SFM™ and a new feeding
                      strategy, we demonstrate a yield boost by a mean of 0.3 log
                      while reducing seeding density to 5.0E3 cells/cm2 and
                      cutting FBS supplementation by up to $40\%$ during the
                      production process. Additionally, FBS is completely removed
                      at the time of harvest. Eleven commercial micro- and
                      macrocarriers were screened regarding cell growth,
                      bead-to-bead transfer capability, and virus yield. We
                      present a proof-of-concept study for producing H-1PV on a
                      large scale with the microcarrier Cytodex® 1 in suspension
                      and a macrocarrier for a fixed-bed iCELLis® bioreactor. A
                      carrier-based H-1PV production process combined with an
                      optimized cell culture medium and feeding strategy can
                      facilitate future upscaling to industrial-scale production.
                      KEY POINTS: • Virus yield increase and FBS-free harvest
                      after switching to cell culture medium VP-SFM™. • We
                      screened carriers for cell growth, bead-to-bead transfer
                      capability, and H-1PV yield. • High virus yield is
                      achieved with Cytodex® 1 and macrocarrier for iCellis® in
                      Erlenmeyer flasks.},
      keywords     = {Bead-to-bead transfer (Other) / Macrocarrier (Other) /
                      Microcarrier (Other) / Protoparvovirus H-1PV production
                      (Other) / Scale-up (Other) / Serum-free (Other)},
      cin          = {F010},
      ddc          = {570},
      cid          = {I:(DE-He78)F010-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34782922},
      doi          = {10.1007/s00253-021-11642-y},
      url          = {https://inrepo02.dkfz.de/record/177493},
}