A decade ago, the evolution of immuno-oncology altered the therapeutic landscape for patients with a variety of cancers. Although individual immunotherapies have improved patient outcomes, the addition of rational combinations of multiple immunotherapy regimens has resulted in more treatment options and the possibility of longer survival.
These advances, however, have not reached all patients, and there is an urgent need to achieve more.
Bristol Myers Squibb was a pioneer in bringing immunotherapy, including dual immunotherapy combinations, to patients, and it continues to investigate the immune system from various angles in order to find potentially complementary combinations of therapies.
Overcoming immune inhibition
Bristol-Myers Squibb has tried a variety of approaches to address the immune response and use it to attack tumors. CTLA-4 and PD-1 are immune checkpoints that inhibit the immune response and help to keep the immune system in check in healthy people. Tumor cells in cancer patients may be able to manipulate immune checkpoints in order to avoid being attacked by T cells, or the body's immune response. Existing therapies have successfully used immune checkpoint inhibition to release the "brakes" from T cells, allowing them to recognize and attack tumors.
LAG-3 is another immune checkpoint that is being studied at Bristol Myers Squibb. LAG-3, a protein found on the surface of some T cells, may promote T cell exhaustion, allowing tumours to avoid detection by the immune system. Blocking the LAG-3 receptor on T cells may help them overcome exhaustion, which is another way of releasing the "brakes" from T cells, according to researchers.
The strategy of using LAG-3 to fight cancer appears to be especially promising when combined with existing immunotherapies. The decision to pursue various combinations is based on scientific reasoning and extensive knowledge of how different mechanisms of action interact.
Bristol-Myers Squibb is investigating doublet and triplet combinations that combine LAG-3 with currently available therapies. We believe there is an opportunity to leverage therapies that have similar mechanisms of action as well as those that have complementary mechanisms of action.
Immunostimulatory Therapy
Immunotherapies that directly stimulate the immune system, as opposed to those that work by overcoming immune response inhibition, have also received attention in research. Therapies that use the IL-2 pathway, for example, may directly activate or antagonise the immune system. They put "gas" in the immune system.
“We believe that immunostimulatory therapies may show promise when used in combination with existing therapies that overcome immune inhibition. We are well positioned to bring these types of dual immunotherapy regimens forward,” said Gary Grossfeld, Global Development Project Leader at Bristol Myers Squibb.
“Leveraging more than one pathway can potentially improve the immune system response to cancer, thereby building on the efficacy of single agent therapy while maintaining a favorable safety profile.”
Part of the process of developing new therapies is ensuring that they are targeted to specific diseases and patient populations.
Certain biomarkers, whether genetic or protein-based, may indicate that one type of therapy or combination will be more effective in some patients than others.
“Our study protocols are filled with exploratory biomarker work aimed at understanding which patients are likely to benefit from certain treatments. We are dedicated to a precision medicine approach in our development programs, and I expect we may see great progress in the next several years,” said Grossfeld.
Grossfeld believes that Bristol Myers Squibb has advanced immuno-oncology research by focusing on precision medicine and taking a strategic approach to enhancing existing therapies with investigational agents. Despite advances in cancer immunotherapy treatment, there are still many unmet clinical needs. The goal is always to make a difference for patients.
These advances, however, have not reached all patients, and there is an urgent need to achieve more.
Bristol Myers Squibb was a pioneer in bringing immunotherapy, including dual immunotherapy combinations, to patients, and it continues to investigate the immune system from various angles in order to find potentially complementary combinations of therapies.
Overcoming immune inhibition
Bristol-Myers Squibb has tried a variety of approaches to address the immune response and use it to attack tumors. CTLA-4 and PD-1 are immune checkpoints that inhibit the immune response and help to keep the immune system in check in healthy people. Tumor cells in cancer patients may be able to manipulate immune checkpoints in order to avoid being attacked by T cells, or the body's immune response. Existing therapies have successfully used immune checkpoint inhibition to release the "brakes" from T cells, allowing them to recognize and attack tumors.
LAG-3 is another immune checkpoint that is being studied at Bristol Myers Squibb. LAG-3, a protein found on the surface of some T cells, may promote T cell exhaustion, allowing tumours to avoid detection by the immune system. Blocking the LAG-3 receptor on T cells may help them overcome exhaustion, which is another way of releasing the "brakes" from T cells, according to researchers.
The strategy of using LAG-3 to fight cancer appears to be especially promising when combined with existing immunotherapies. The decision to pursue various combinations is based on scientific reasoning and extensive knowledge of how different mechanisms of action interact.
Bristol-Myers Squibb is investigating doublet and triplet combinations that combine LAG-3 with currently available therapies. We believe there is an opportunity to leverage therapies that have similar mechanisms of action as well as those that have complementary mechanisms of action.
Immunostimulatory Therapy
Immunotherapies that directly stimulate the immune system, as opposed to those that work by overcoming immune response inhibition, have also received attention in research. Therapies that use the IL-2 pathway, for example, may directly activate or antagonise the immune system. They put "gas" in the immune system.
“We believe that immunostimulatory therapies may show promise when used in combination with existing therapies that overcome immune inhibition. We are well positioned to bring these types of dual immunotherapy regimens forward,” said Gary Grossfeld, Global Development Project Leader at Bristol Myers Squibb.
“Leveraging more than one pathway can potentially improve the immune system response to cancer, thereby building on the efficacy of single agent therapy while maintaining a favorable safety profile.”
Part of the process of developing new therapies is ensuring that they are targeted to specific diseases and patient populations.
Certain biomarkers, whether genetic or protein-based, may indicate that one type of therapy or combination will be more effective in some patients than others.
“Our study protocols are filled with exploratory biomarker work aimed at understanding which patients are likely to benefit from certain treatments. We are dedicated to a precision medicine approach in our development programs, and I expect we may see great progress in the next several years,” said Grossfeld.
Grossfeld believes that Bristol Myers Squibb has advanced immuno-oncology research by focusing on precision medicine and taking a strategic approach to enhancing existing therapies with investigational agents. Despite advances in cancer immunotherapy treatment, there are still many unmet clinical needs. The goal is always to make a difference for patients.