Scholarlink

<p>Progress in immunotherapy treatment with cancer depends on perfecting methods to culture patient-derived Cytotoxic T Lymphocytes (CTLs). We report on use of a prototype centrifugal bioreactor (CBR) for the first time with a human cell line (leukemia cells) and O<sub>2</sub> sensors to assure sufficient respiration. We maintained O<sub>2</sub> levels using a high recycle rate, circulating recycled medium through a humidified 95%:5% air: CO<sub>2</sub> gas stream. We improved system modeling using a fed-batch approach for expanding cells while at the same time using CSTR (Continuous Stirred Tank Reactor) modeling for nutrient and metabolites. Monod kinetic parameters were determined with a maximum specific growth rate, <i>µ</i><sub><i>max</i></sub>, of 0.0243&#xa0;h<sup>− 1</sup>, and Monod constant, <i>K</i><sub><i>M</i></sub>, of 1.78&#xa0;mg/dL. Modeling tracks experimental data to within 10%, reaching a total of 129&#xa0;million cells in our 11 mL CBR with inconsequential levels of toxic metabolites. Extension of our model provides supportive evidence that the existing CBR can produce higher cell numbers, up to 5.8&#xa0;billion cells in 9.2 days achieving a high population density of 12% cells in a future CBR retrofitted for higher revolutions per minute (RPM). Predictions of extension to these ultra-high densities provide promise for higher yields of CAR-T and other cell product applications for the CBR.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A centrifugal bioreactor for immunotherapy: modeling and optimization of the growth of human T lymphoblastic leukemia cells

  • 期刊论文

  • 发表日期：

    2026年6月15日

查看全文
  • Brenden Fraser-Hevlin,
  • Kitana M. Kaiphanliam,
  • Zakora Moore,
  • William C. Davis,
  • Bernard J. Van Wie

摘要

Progress in immunotherapy treatment with cancer depends on perfecting methods to culture patient-derived Cytotoxic T Lymphocytes (CTLs). We report on use of a prototype centrifugal bioreactor (CBR) for the first time with a human cell line (leukemia cells) and O2 sensors to assure sufficient respiration. We maintained O2 levels using a high recycle rate, circulating recycled medium through a humidified 95%:5% air: CO2 gas stream. We improved system modeling using a fed-batch approach for expanding cells while at the same time using CSTR (Continuous Stirred Tank Reactor) modeling for nutrient and metabolites. Monod kinetic parameters were determined with a maximum specific growth rate, µmax, of 0.0243 h− 1, and Monod constant, KM, of 1.78 mg/dL. Modeling tracks experimental data to within 10%, reaching a total of 129 million cells in our 11 mL CBR with inconsequential levels of toxic metabolites. Extension of our model provides supportive evidence that the existing CBR can produce higher cell numbers, up to 5.8 billion cells in 9.2 days achieving a high population density of 12% cells in a future CBR retrofitted for higher revolutions per minute (RPM). Predictions of extension to these ultra-high densities provide promise for higher yields of CAR-T and other cell product applications for the CBR.