The incident happened on the corner of Apex and Apex roads, just before 10am.
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Maj-Gen Poobalan Subbiah, the Ekurhuleni Central Cluster commander, said explosives were used to blow up the cash-in-transit vehicle.
No injuries have been reported.
Subbiah said police are not only searching for five people, but also three vehicles believed to have been used in the crime.
They made off with an undisclosed amount of money.
The armed criminals are being persued by police, with the aid of a helicopter which is searching for them.
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