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Small-scale manufacturing of neoantigen-encoding messenger RNA for early-phase clinical trials

Joline Ingels (UGent) , Laurenz De Cock (UGent) , Rupert Mayer (UGent) , Pam Devreker (UGent) , Karin Weening (UGent) , Kelly Heyns (UGent) , Nele Lootens (UGent) , Saskia De Smet (UGent) , Marieke Brusseel (UGent) , Stijn De Munter (UGent) , et al.
(2022) CYTOTHERAPY. 24(2). p.213-222
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Abstract
Messenger RNA (mRNA) has become a promising tool in therapeutic cancer vaccine strategies. Owing to its flexible design and rapid production, mRNA is an attractive antigen delivery format for cancer vaccines targeting mutated peptides expressed in a tumor-the so-called neoantigens. These neoantigens are rarely shared between patients, and inclusion of these antigens in a vaccine requires the production of individual batches of patient-tailored mRNA. The authors have developed MIDRIXNEO, a personalized mRNA-loaded dendritic cell vaccine targeting tumor neoantigens, which is currently being evaluated in a phase 1 clinical study in lung cancer patients. To facilitate this study, the authors set up a Good Manufacturing Practice (GMP)-compliant production process for the manufacture of small batches of personalized neoantigenencoding mRNA. In this article, the authors describe the complete mRNA production process and the extensive quality assessment to which the mRNA is subjected. Validation runs have shown that the process delivers mRNA of reproducible, high quality. This process is now successfully applied for the production of neoantigen-encoding mRNA for the clinical evaluation of MIDRIXNEO. To the authors' knowledge, this is the first time that a GMP-based production process of patient-tailored neoantigen mRNA has been described. (c) 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article
Keywords
good manufacturing practices, messenger RNA, neoantigens, vaccines, Introduction, IDENTIFICATION, THERAPEUTICS, MUTANOME, IMMUNITY

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MLA
Ingels, Joline, et al. “Small-Scale Manufacturing of Neoantigen-Encoding Messenger RNA for Early-Phase Clinical Trials.” CYTOTHERAPY, vol. 24, no. 2, 2022, pp. 213–22, doi:10.1016/j.jcyt.2021.08.005.
APA
Ingels, J., De Cock, L., Mayer, R., Devreker, P., Weening, K., Heyns, K., … Vandekerckhove, B. (2022). Small-scale manufacturing of neoantigen-encoding messenger RNA for early-phase clinical trials. CYTOTHERAPY, 24(2), 213–222. https://doi.org/10.1016/j.jcyt.2021.08.005
Chicago author-date
Ingels, Joline, Laurenz De Cock, Rupert Mayer, Pam Devreker, Karin Weening, Kelly Heyns, Nele Lootens, et al. 2022. “Small-Scale Manufacturing of Neoantigen-Encoding Messenger RNA for Early-Phase Clinical Trials.” CYTOTHERAPY 24 (2): 213–22. https://doi.org/10.1016/j.jcyt.2021.08.005.
Chicago author-date (all authors)
Ingels, Joline, Laurenz De Cock, Rupert Mayer, Pam Devreker, Karin Weening, Kelly Heyns, Nele Lootens, Saskia De Smet, Marieke Brusseel, Stijn De Munter, Melissa Pille, Lore Billiet, Glenn Goetgeluk, Sarah Bonte, Hanne Jansen, Sandra Van Lint, Georges Leclercq, Tom Taghon, Björn Menten, Karim Vermaelen, Francis Impens, and Bart Vandekerckhove. 2022. “Small-Scale Manufacturing of Neoantigen-Encoding Messenger RNA for Early-Phase Clinical Trials.” CYTOTHERAPY 24 (2): 213–222. doi:10.1016/j.jcyt.2021.08.005.
Vancouver
1.
Ingels J, De Cock L, Mayer R, Devreker P, Weening K, Heyns K, et al. Small-scale manufacturing of neoantigen-encoding messenger RNA for early-phase clinical trials. CYTOTHERAPY. 2022;24(2):213–22.
IEEE
[1]
J. Ingels et al., “Small-scale manufacturing of neoantigen-encoding messenger RNA for early-phase clinical trials,” CYTOTHERAPY, vol. 24, no. 2, pp. 213–222, 2022.
@article{8738039,
  abstract     = {{Messenger RNA (mRNA) has become a promising tool in therapeutic cancer vaccine strategies. Owing to its flexible design and rapid production, mRNA is an attractive antigen delivery format for cancer vaccines targeting mutated peptides expressed in a tumor-the so-called neoantigens. These neoantigens are rarely shared between patients, and inclusion of these antigens in a vaccine requires the production of individual batches of patient-tailored mRNA. The authors have developed MIDRIXNEO, a personalized mRNA-loaded dendritic cell vaccine targeting tumor neoantigens, which is currently being evaluated in a phase 1 clinical study in lung cancer patients. To facilitate this study, the authors set up a Good Manufacturing Practice (GMP)-compliant production process for the manufacture of small batches of personalized neoantigenencoding mRNA. In this article, the authors describe the complete mRNA production process and the extensive quality assessment to which the mRNA is subjected. Validation runs have shown that the process delivers mRNA of reproducible, high quality. This process is now successfully applied for the production of neoantigen-encoding mRNA for the clinical evaluation of MIDRIXNEO. To the authors' knowledge, this is the first time that a GMP-based production process of patient-tailored neoantigen mRNA has been described. (c) 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access article}},
  author       = {{Ingels, Joline and De Cock, Laurenz and Mayer, Rupert and Devreker, Pam and Weening, Karin and Heyns, Kelly and Lootens, Nele and De Smet, Saskia and Brusseel, Marieke and De Munter, Stijn and Pille, Melissa and Billiet, Lore and Goetgeluk, Glenn and Bonte, Sarah and Jansen, Hanne and Van Lint, Sandra and Leclercq, Georges and Taghon, Tom and Menten, Björn and Vermaelen, Karim and Impens, Francis and Vandekerckhove, Bart}},
  issn         = {{1465-3249}},
  journal      = {{CYTOTHERAPY}},
  keywords     = {{good manufacturing practices,messenger RNA,neoantigens,vaccines,Introduction,IDENTIFICATION,THERAPEUTICS,MUTANOME,IMMUNITY}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{213--222}},
  title        = {{Small-scale manufacturing of neoantigen-encoding messenger RNA for early-phase clinical trials}},
  url          = {{http://dx.doi.org/10.1016/j.jcyt.2021.08.005}},
  volume       = {{24}},
  year         = {{2022}},
}

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