التفاصيل البيبلوغرافية
| العنوان: |
GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2. |
| المؤلفون: |
Mizrahi, Rena A., Lin, Wendy Y., Gras, Ashley, Niedecken, Ariel R., Wagner, Ellen K., Keating, Sheila M., Ikon, Nikita, Manickam, Vishal A., Asensio, Michael A., Leong, Jackson, Medina-Cucurella, Angelica V., Benzie, Emily, Carter, Kyle P., Chiang, Yao, Edgar, Robert C., Leong, Renee, Lim, Yoong Wearn, Simons, Jan Fredrik, Spindler, Matthew J., Stadtmiller, Kacy |
| المصدر: |
Pathogens; Jul2022, Vol. 11 Issue 7, pN.PAG-N.PAG, 17p |
| مصطلحات موضوعية: |
GLOBULINS, ANTIBODY diversity, SARS-CoV-2, CURRENT good manufacturing practices, INVESTIGATIONAL drugs, IMMUNOGLOBULINS, PLANT protection, MONOCLONAL antibodies |
| مستخلص: |
Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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