An antibody-drug conjugate (ADC), such as a TAP compound, has three key components –
		The cell-killing agent,
		the attachment between it and the tumor-targeting antibody,
		and the antibody itself.

The Cell-Killing Agent

ImmunoGen has developed cell-killing (cytotoxic) agents that are designed specifically for delivery to cancer cells attached to antibodies.

In contrast to traditional chemotherapeutic agents, which are small molecules, antibodies are large molecules. So, only a small amount of an administered antibody successfully penetrates inside a solid tumor – the rest remains circulating in the blood stream until removed by the body. Consequently, only a small amount of any agent attached to an antibody will reach the cancer cells in a solid tumor. This means that the attached agent must be highly potent – able to kill when present at very low levels. ImmunoGen addressed this by identifying one of the few ultra-potent cytotoxic agents that exists, maytansine, and carefully modifying it to enable its attachment to and release from an antibody without loss of potency – a formidable challenge.

Our proprietary cell-killing agents (e.g., DM1, DM4) are 1,000- to 10,000-fold more potent than traditional chemotherapeutics. Over time, we have developed a portfolio of these agents that enables us – and our partners – to select the agent that provides the best performance for each antibody and its target.

Attachment to the Antibody

The bond used to attach the cytotoxic agent to the antibody must stay intact while the ADC is circulating in the patient’s bloodstream, but enable the agent to kill a cancer cell once inside it.

This bond is formed between the cytotoxic agent (e.g., our DM1) and the “linker” that we place on the antibody for attachment of the agent. Consequently, we determine this bond by the design of our cell-killing agents and the linkers we use with them.

Our portfolio of cytotoxic agents and of linkers enables us to achieve alternative bonds that differ in their resistance to breakage, which is important when tailoring a TAP compound to optimize performance. We can form disulfide bonds with increasing degrees of resistance to breakage inside a cancer cell. We also can make a non-disulfide bond that is particularly resistant to breakage.

The Antibody

The monoclonal antibody component of an ADC is what enables the compound to bind specifically to cancer cells and so these antibodies must be to targets that occur predominantly on cancer cells. With our own TAP compounds, the antibody has been developed or in-licensed by ImmunoGen. Alternatively, the antibody may be one that wasn’t available for our own programs and belongs to a collaborator that has licensed the right to use our TAP technology.

While ImmunoGen is known for our TAP technology, we also have extensive antibody expertise. For example, we are experienced in the evaluation of potential cancer targets and in the development of high-quality antibodies to these targets. We have proprietary humanization technology which enables us to modify non-human antibodies to avoid detection by a patient’s immune system. And we can develop cell lines capable of producing substantial quantities of an antibody in a manufacturing setting.

Every TAP compound that enters development reflects our extensive expertise in the many facets of ADC design and the quality of our TAP technology.

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