Anti-cancer advanced modalities

Video transcript 

(light music) [Narrator]

Cancer is a complex and heterogeneous disease that can become aggressive and resist treatment. That's why researchers are working to develop new treatments that interfere with cancer processes using advanced 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.

Antibody drug conjugates, protein degraders, and chimeric antigen receptor, or CAR, T cell therapy are just three of the primary methods we use to target and kill cancer cells.

Critical components of BMS’ modality toolbox include precision-based approaches — such as antibody-drug conjugates, or ADCs, and radiopharmaceutical therapies or RPTs. These modalities have already shown practice-changing results and are poised to deliver innovation in the future of cancer therapy.

Let’s take a closer look at ADCs. ADCs consist of three elements: the monoclonal antibody that 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 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.

Protein degradation is another example of an anti-cancer modality. Let’s take a closer look.

Targeted protein degradation is an approach that has been used to treat certain cancers for decades and harnesses the cell’s own machinery to degrade disease-causing proteins that may otherwise be hard to target using traditional modalities.

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

Once the target protein is brought into contact with the ligase, the E3 ligase tags the target for destruction by a protein complex called the proteasome.

BMS scientists carefully design these degraders to target specific harmful disease-causing proteins, which ultimately leads to their destruction.

Researchers at BMS are leveraging three methods of protein degradation: molecular glues, or CELMoD agents, ligand-directed degraders, or LDDs, which are 3-part molecules, and degrader-antibody conjugates, or DACs, which are CELMoD agents attached to an antibody to precisely deliver the therapeutic payload. All methods bring the target of interest into proximity with the protein degradation machinery, or ligase, resulting in target destruction. This three-pronged approach ultimately provides more opportunities for breakthroughs that may offer meaningful new treatment options for patients across a broad range of diseases.

Finally, CAR T cell therapy is a type of immunotherapy that reprograms T cells (or fighter cells) to recognize and bind to proteins (specific antigens) found on the surface of certain cells.

CAR T cells are created by using a viral vector to insert a gene that encodes the CAR into the T cells.

CARs are a specialized receptor that both recognizes cancer cells and provides activating signaling components inside the T cell.

Millions of the engineered CAR T cells are grown in a strictly controlled manufacturing facility and then infused into the patient.

The CAR T cells then recognize and bind to cancer cells resulting in cancer cell death.

Research suggests that, with a single treatment, CAR T cell therapy has been effective at producing clinically meaningful, deep and durable responses in patients where other treatment options have stopped working.

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.