Why are monoclonal antibodies (mAbs) from hybridoma or CHO cultures typically produced in fed-batch mode? Focus on how glucose feeding limits lactate accumulation and supports productivity.
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AHybridoma cells ferment mainly on maltose at high concentrations
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BHybridoma cells yield higher lactate at high glucose concentrations, so controlled feeding reduces lactate
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CHybridoma cells switch to pure respiration at high glucose concentrations
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DNone of the above
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EFed-batch is used only to avoid shear, not metabolism
Answer
Correct Answer: Hybridoma cells yield higher lactate at high glucose concentrations, so controlled feeding reduces lactate
Explanation
Introduction / Context:Most industrial monoclonal antibody (mAb) processes use fed-batch operation with mammalian cells (hybridoma or CHO). A key reason is metabolic: excessive glucose drives aerobic glycolysis with high lactate formation, which can depress pH control, osmolarity, and specific productivity. Controlled feeding maintains glucose in a narrow band to limit lactate build-up and sustain viable, productive cultures.
Given Data / Assumptions:
- Mammalian cells exhibit a Warburg-like effect: at high glucose, they produce lactate even under aerobic conditions.
- High lactate and acidification reduce viability and mAb quality attributes if unmanaged.
- Fed-batch allows tight control of extracellular glucose concentration.
Concept / Approach:By delivering nutrient feeds gradually, fed-batch prevents large glucose spikes. The culture consumes glucose close to its uptake rate, reducing the driving force for overflow metabolism to lactate. This stabilizes pH control (less base addition), improves viable cell days, and supports sustained antibody secretion phases.
Step-by-Step Solution:1) Identify the metabolic issue: high glucose → high lactate via aerobic glycolysis.2) Choose a mode that avoids spikes: fed-batch with feedback or predefined boluses.3) Observe improved metrics: lower lactate, higher viability, longer production window, better titer.4) Conclude that feed strategy is central to modern mAb platforms.
Verification / Alternative check:Process data commonly show lactate peaking early in batch but remaining controlled in fed-batch; some platforms harness lactate consumption phases when glucose is held low later in culture.
Why Other Options Are Wrong:Option A misidentifies the sugar and mechanism; maltose is not the typical driver. Option C is the inverse of reality; high glucose favors lactate, not pure respiration. Option D is incorrect because B is valid; Option E ignores the dominant metabolic motivation.
Common Pitfalls:Assuming more glucose always raises productivity; beyond a point, it worsens lactate and osmolality.
Final Answer:Hybridoma cells yield higher lactate at high glucose concentrations, so controlled feeding reduces lactate