In 2006, TGN 1412, a super-agonist antibody targeting the
immune system, was administered to six healthy volunteers in a Phase I clinical
trial. Unexpectedly, the drug triggered a cytokine storm, leading to
multi-organ failure.

Considering what is known about pre-clinical testing and
species differences, which explanation MOST LOGICALLY accounts for why this
severe immune toxicity was not predicted before human trials?

Question

In 2006, TGN 1412, a super-agonist antibody targeting the
immune system, was administered to six healthy volunteers in a Phase I clinical
trial. Unexpectedly, the drug triggered a cytokine storm, leading to
multi-organ failure.

Considering what is known about pre-clinical testing and
species differences, which explanation MOST LOGICALLY accounts for why this
severe immune toxicity was not predicted before human trials?

Accepted Answer

Animal
models were used in which the immune system responds differently to TGN 1412
than in humans, making severe toxicity undetectable

Answer

TGN
1412 was administered via a different route in animals than in humans,
preventing a comparable immune response

Answer

Pre-clinical
studies tested lower doses than those used in humans, so toxicity at higher
doses was missed

Answer

Only
a single dose was tested in animals, so dose-dependent toxicity could not be
observed

Crowdly

In 2006, TGN 1412, a super-agonist antibody targeting the immune system, was ad...

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