Anti-cancer advanced modalities

See how we're working to transform cancer treatment with investigational anti-cancer modalities: immune cell engagers, antibody-drug conjugates & targeted protein degradation.

Video transcript 

(light music) [Narrator]

Cancer is a complex and heterogeneous disease with an inherent drive to spread throughout the body and resist treatment.

Researchers work to interfere with cancer processes usingadvanced anti-cancer modalities, which recognize and eliminate cancer cells in diverse ways.

BMS is building upon its legacy of leadership in cancer treatment with a robust and ever-growing arsenal of modalities from small molecules to complex biologics and cell therapies, immune cell engagers, antibody-drug conjugates, and protein degraders are just three of the methods we useto target and kill cancer cells.

Let's take a closer look at immune cell engagers or ICEs. Immune cell engagers are engineered as multi specific molecules.

One side binds to one or more tumor associated antigens on the surface of the cancer cell, and the other side binds to molecules on the surface of an immune cell, such as a T cell or a natural killer cell.

Binding of the engager facilitates an interaction between the tumor cell and the immune cell through an immunological synapse, an area between cells where molecular interactions can take place.

The immune cell can not target the cancer cell for destruction.

Next, antibody-drug conjugates consist of three elements.

The monoclonal antibod that's specifically targets cancer cells.

The payload often called a warhead, which is a medicine and a linker that connects the two. Researchers are exploring next generation ADCs that replace the standard payload with other medicines.

These can include optimized cytotoxic payloads and novel small molecule payloads like an immune agonist, small molecule inhibitor, or a protein degrader.

Linkers are a key component in the function of antibody drug conjugates, providing high stability in circulation and specific release of the payload in the target tissue.

For example, optimized antibody-drug conjugates carrying a traditional cytotoxic payload are designed to target and bind to specific cancer cell antigens and form an antibody-drug conjugate antigen complex which is then taken into the cell. 

This is followed by the breakdown of the complex, which results in the release of the payload into the cancer cell, causing cancer cell death.

This precision-based approach with novel selective linkers allows targeted drug delivery with more stable technology to effectively deliver targeted drugs directly to cancer cells while relatively sparing normal cells.

Protein degradation is another example of an anti-cancer modality. 

Let's take a closer look.

Targeted protein degradation is an approach that harnesses the cell's own machinery to degrade disease causing proteins that may otherwise be hard to target using traditional modalities.

Researchers at BMS are leveraging three methods of protein degradation, molecular glues, or cell mod agents, ligand-directed degraders or LDDs and antibody-drug conjugate degraders.

All methods bring the target of interest into proximity with the protein degradation tagging machinery or ligase, resulting in target destruction.

Protein degraders are small molecules that work by promoting direct interactions between the target protein and a ubiquitin ligase enzyme, which would not otherwise interact.

Scientists look for and design protein degraders that target specific disease causing proteins to be broken down.

Once a target protein is brought into contact with the ligase, the target protein is tagged for removal by the ligase and degraded by an enzyme called the proteasome.

This ultimately results in the destruction of the disease-causing protein.

At Bristol Myers Squibb, we are driven by a deep understanding of causal human biology and the complexities of cancer.

We are purposefully exploring numerous anti-cancer approaches to modulate and affect cancer targets with a strategic approach to match therapeutic modality to molecular mechanism of action.