Amplimmune specialises in developing treatments designed to help the immune system fight cancer and the purchase will give AstraZeneca access to a number of compounds currently in pre-clinical development.
While it will not yield commercially viable new medicines for several years, the move fits with the British drugmaker's strategy of building up its capability in oncology - a key area identified for investment by chief executive Pascal Soriot.
AstraZeneca's MedImmune biotech unit will acquire 100% of Amplimmune's shares for an initial $225m and a deferred consideration of up to $275m based on reaching predetermined development milestones.
Bahija Jallal, executive vice president of MedImmune, said: "It will allow us to strengthen our arsenal of potential cancer therapies."
AstraZeneca already has other immune-mediated cancer therapies in clinical development and its decision to place a further bet on early research reflects its determination to compete with companies such as Roche Holding AG and Merck & Co in a hot area of cancer research.
The new wave of medicines that tap the power of the immune system to fight cancer could become the biggest drug class in history, with potential sales of $35 billion a year, according to analysts at US bank Citigroup.
The deal is the second in the cancer drug space in recent days, following Amgen's acquisition of Onyx Pharmaceuticals for about $10.4bn.