Explore our Comprehensive Approach to Cancer Research
At Bristol Myers Squibb, we are driven to understand human biology and the complexities of cancer in order to advance the next generation of cancer therapies. Our comprehensive pipeline, spanning multiple approaches across platforms and modalities, enables us to fulfill our vision of transforming patients’ lives through science.
Bristol Myers Squibb is
leading advancements in:
- Immuno-
Oncology - Cell
Therapy - Protein
Degradation
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Using multiple approaches to advance the next generation of cancer therapies
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Improve recognition of cancer cells
The immune system naturally defends and protects the body against infection, involving a complex network of cells and signaling molecules. Bristol Myers Squibb is investigating multiple pathways and targets with the aim of amplifying the ability of the immune system to recognize and eliminate cancer cells.
- SIRPα
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- SIRPα is an inhibitory receptor expressed on macrophages and dendritic cells.1-3
- CD47, a protein found on the surface of cells, binds SIRPα, initiating an inhibitory signaling pathway that helps maintain immunotolerance to normal cells.1-3
- In cancer, overexpression of CD47 on the surface of tumor cells allows tumors to escape detection, acting as a “don’t eat me” signal, limiting the anti-cancer immune response.1-3
- Inhibition of the CD47-SIRPα signaling pathway is intended to improve the recognition and enhance phagocytosis of cancer cells by macrophages.4
- Fucosyl-GM1
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- Targeting the fucosyl-GM1 tumor-associated antigen is intended to improve the recognition of cancer cells by phagocytes and natural killer (NK) cells.1,2
- STING
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- Activation of the STING pathway, which induces the production of cytokines, is intended to improve recognition of tumor cells by stimulating an innate and adaptive anti-cancer response.1,2
- CD47
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- CD47, a protein found on the surface of cells, binds SIRPα, initiating an inhibitory signaling pathway that helps maintain immunotolerance to normal cells.1-3
- In cancer, overexpression of CD47 on the surface of tumor cells allows tumors to escape detection, acting as a “don’t eat me” signal, limiting the anti-cancer immune response.1-3
- Inhibition of the CD47-SIRPα signaling pathway is intended to improve the recognition and enhance phagocytosis of cancer cells by macrophages.4
- CD20
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- CD20 is a protein found on the surface of normal and cancerous B lymphocytes, a type of white blood cell.1
- Dual engagement of the CD47/SIRPa pathway and CD20 on tumor cells can lead to cell destruction.1
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Prevent immunosuppression
The tumor microenvironment (TME) contains cells and signaling molecules that suppress an anti-tumor immune response. Bristol Myers Squibb is investigating ways to block the tumor’s ability to recruit immunosuppressive cell types to the TME and inhibit signaling that contributes to immunosuppression.
- CTLA-4
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- CTLA-4 is an immune checkpoint receptor found on the surface of effector T cells and on regulatory T cells (Tregs).1,2
- When the CTLA-4 pathway is engaged, Tregs in the TME suppress the immune response, inhibiting T cell activation.3
- Targeting CTLA-4 with antibodies designed to deplete Tregs in the TME is intended to increase the anti-cancer immune response.4
- IL-8
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- The release of IL-8 by cancer cells promotes immune evasion by recruiting immunosuppressive cell types to the TME, thereby reducing immune response against the tumor.1
- Prevention of IL-8 signaling is intended to inhibit the recruitment of immunosuppressive cell types to the TME.2
- CCR8
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- is a protein found mainly on the surface of regulatory T cells (Tregs) within tumors and is a regulator of immune response.1,2
- CCR8 is upregulated on a highly immunosuppressive subset of Tregs in multiple cancer types.2,3
- Targeting CCR8 is intended to deplete Tregs and drive a pro-inflammatory response, resulting in inhibition of tumor growth.3
- TGF-β1 and TGF-β3
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- TGF-β is a critical mediator of immuno-oncology resistance.1,3
- Neutralization of cytokines TGF-β1 and TGF-β3 is intended to decrease immune exclusion and increase effector cell function.1,2
- ILT4
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- ILT4 is an immunosuppressive molecule expressed in myeloid cells and present in the tumor microenvironment (TME).1
- Inhibition of the ILT4 receptor is intended to promote a proinflammatory response and result in subsequent cancer cell death.1
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Enhance effector cell function
Cancer cells can suppress effector cells (short-lived activated cells of the immune system), but these cells can also be modified to mount a cytotoxic attack. Bristol Myers Squibb is investigating ways to increase the ability of effector cells to act on cancer cells, direct cytotoxic activity toward cancer cells and engineer cell therapies that exhibit continued anti-cancer activity.
- CTLA-4
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- CTLA-4 is an immune checkpoint receptor found on the surface of activated T cells.1,2
- Cancer cells use the CTLA-4 pathway to decrease T cell activation, proliferation and effector function—effectively turning “off” the immune response.3,4
- Bristol Myers Squibb pioneered the first approved immune checkpoint inhibitor, a monoclonal antibody targeting CTLA-4, which ushered in a historic era of harnessing the immune system to treat cancer and ignited exploration into the TME.
- Researchers are exploring strategies to optimize the CTLA-4 blockade by building on the existing CTLA-4 science through second- and next- generation compounds, with a goal of improving the risk-benefit profile of CTLA-4–directed therapy.5,6
- NKG2-A
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- Inhibition of NKG2-A is intended to enhance effector cell function by blocking the inhibitory NKG2-A immune checkpoint signaling pathway.1,2
- TIGIT
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- Inhibition of TIGIT is intended to restore effector cell function by blocking the inhibitory TIGIT immune checkpoint signaling pathway.1,2
- AHR
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- Inhibitors of AHR are intended to block the activation of the AHR pathway—a pathway that promotes immunosuppression and immune cell dysfunction—leading to enhanced effector cell function.1,2
- Activated AHR is also associated with resistance to immune checkpoint blockade.2
- IL-12
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- IL-12 is a proinflammatory cytokine that plays a central role in regulating both innate and adaptive anti-tumor immune response.1
- IL-12 stimulates innate and adaptive immunity through increasing effector T cell and natural killer (NK) cell activity and IFN-γ production.1
- IL-12 agonism is intended to stimulate effector cell activation and proliferation1
- BCMA
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- BCMA is a transmembrane protein that plays a key role in the proliferation, maturation and differentiation of B cells into plasma cells and is important for plasma cell survival.1
- BCMA can be overexpressed in cancer cells.2
- BCMA can be targeted using multiple types of anti-cancer therapeutics, such as cell therapies, recognizing the BCMA receptor and subsequently killing the cancer cell.1,3,4
- CD19
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- CD19 is a protein that is expressed in B-cell malignancies, including multiple cancer types.1,2
- CD19 can be targeted using multiple types of anti-cancer therapeutics, such as cell therapies, recognizing the CD19 receptor and subsequently killing the cancer cell.3
- MAGE A4/8
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- MAGE A4/8 is a highly prevalent antigen present in multiple solid tumors.1
- MAGE A4/8 can be targeted using anti-cancer therapies such as cell therapies, immune engagers and antibody drug conjugates, which recognize the antigen and subsequently kill the cancer cell.1
- ROR1
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- ROR1 is overexpressed in many tumor types and plays a key role in cancer cell survival signaling.1
- ROR1 can be targeted using anti-cancer therapies such as cell therapies, immune engagers and antibody drug conjugates, which recognize the antigen and subsequently kill the cancer cell.1
- CD33
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- CD33 is a protein that is expressed on acute myeloid leukemia cells.1
- CD33 can be targeted using anti-cancer therapies such as cell therapies, immune engagers and antibody drug conjugates, which recognize the antigen and subsequently kill the cancer cell.1
- GPRC5D
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- GPRC5D is a myeloma cell surface antigen overexpressed by cancer cells and associated with poor prognosis.1
- GPRC5D can be targeted using anti-cancer therapies such as cell therapies, immune engagers and antibody drug conjugates, which recognize the antigen and subsequently kill the cancer cell.1
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Target tumor-intrinsic pathways
Cancer cell growth and survival is dictated by molecular mechanisms within the tumor. Bristol Myers Squibb is working to leverage these various pathways to enhance cancer cell death.
- Aiolos and Ikaros
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- Aiolos and Ikaros regulate gene expression in tumor cells and T cells and contribute to myeloma cell survival.
- The destruction of Aiolos and Ikaros, mediated through protein degradation, is intended to result in cancer cell death and stimulation of immune effector cells.1,2
- With targeted protein degradation, researchers are harnessing cells’ own machinery to degrade several whole new classes of proteins that were previously considered “undruggable.”
- AR
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- Androgen receptor (AR) plays a key role in prostate cancer cell proliferation, but increased AR expression and mutations lead to developed resistance to AR inhibitors.1
- The selective destruction of AR, mediated through protein degradation, is intended to inhibit the proliferation of cancer cells.2,3
- GSPT1
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- GSPT1 plays a key role in the cell life cycle; loss of GSPT1 activates a response leading to cell death.1,2
- The selective destruction of GSPT1, mediated through protein degradation, is intended to lead to cell death.3,4
- With targeted protein degradation, researchers are harnessing cells’ own machinery to degrade several whole new classes of proteins that were previously considered “undruggable.”
- BET
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- Inhibition of the BET pathway, which perpetuates tumor cell growth and survival, is intended to modulate genetic drivers of oncogenesis, leading to a decrease in tumor growth.1,2
- LSD1
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- Inhibition of the LSD1 pathway, which can regulate certain tumor gene expression, is thought to modulate gene expression related to tumor growth, leading to tumor reduction.1,2
- CK1α
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- CK1α is a kinase that influences regulatory proteins involved in multiple signaling pathways important to cancer cells.1,2
- The selective destruction of CK1α, mediated through protein degradation, is intended to inhibit the proliferation of cancer cells.1,2
- DGK
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- DGKs are a family of enzymes that modulate molecules that help regulate T cell activity.1
- Inhibition of DGKs is designed to improve T cell activity in cancer.1
- SHP2
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- SHP2 is a protein phosphatase associated with many types of cancer and is involved in multiple cancer-related processes.1
- SHP2 is an attractive therapeutic target due to its wide-ranging role in cancer survival and growth.1
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With an expansive arsenal of modalities
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Organic compounds that are relatively small in size, usually taken orally and easily absorbed by the body.
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Autologous chimeric antigen receptor (CAR) T cell therapy reprograms immune cells to attack cancer.
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Molecules that redirect the body’s immune response toward cancer cells.
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“Masked” antibodies that are activated within the tumor microenvironment. Designed to limit activity—and toxicity—in healthy tissue.
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Engineered antibodies that can bind to 2 different antigens.
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By tethering a small molecule to a biologic, antibody-drug conjugates are engineered to deliver small molecules to targeted locations using biologic monoclonal antibodies as honing mechanisms.
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