The Power of Dual Immunotherapy

Originally published on Bristol Myers Squibb News & Perspectives

A decade ago, the evolution of immuno-oncology transformed the landscape of therapy for patients with many cancers. Although individual immunotherapies have helped to improve outcomes for patients, the addition of rational combinations of more than one immunotherapy regimen has led to more treatment options and the potential for longer survival.

Not all patients have been reached by these advances though and there is an urgency to achieve more.

Bristol Myers Squibb has been a pioneer in bringing immunotherapy, including dual immunotherapy combinations, forward to patients, and continues to examine the immune system from multiple perspectives in order to find potentially complementary combinations of therapies.

Building upon existing therapies that overcome immune inhibition

Bristol Myers Squibb has pursued a number of ways to address the immune response and leverage it to attack tumors. CTLA-4 and PD-1 are immune checkpoints that inhibit the immune response and, in a healthy person, work to keep the immune system in check. In patients with cancer, tumor cells can potentially manipulate immune checkpoints to evade attack from T cells, or the body’s immune response. Existing therapies have successfully leveraged inhibition of these immune checkpoints to release the “brakes” from T cells and allow them to recognize and to attack tumors.

LAG-3是另一个免疫检查站，它是Bristol Myers Squibb的研究工作重点。LAG-3是在某些T细胞表面发现的蛋白质，可能会促进T细胞耗尽，这可以使肿瘤逃避免疫系统。研究人员发现，在T细胞上阻止LAG-3受体可能有助于他们克服疲惫，这是从T细胞中释放“制动器”的另一种方法。

The strategy of leveraging LAG-3 to fight cancer seems particularly promising when used in combination with existing immunotherapies. The decision to pursue various combinations is made based on scientific rationale and deep knowledge of how different mechanisms of action can work together.

Bristol Myers Squibb is exploring doublet and triplet combinations that bring together LAG-3 with existing therapies. We believe we have the opportunity to leverage therapies with similar mechanisms of action, as well as those with complementary mechanisms of action.

Exploring the promise of immunostimulatory therapy

Research has also focused on immunotherapies that directly stimulate the immune system, as opposed to those that work by overcoming inhibition of the immune response. For example, therapies leveraging the IL-2 pathway may directly activate, or agonize, the immune system. They step on the “gas” of the immune system.

“我们认为，与克服免疫抑制作用的现有疗法结合使用时，免疫刺激性疗法可能会显示出希望。我们有好处，可以将这些类型的双重免疫疗法方向前进。“利用多个途径可以潜在地改善对癌症的免疫系统反应，从而在保持良好的安全性方面建立基于单药疗法的功效。”

The importance of precision medicine

Part of bringing new therapies forward is ensuring that they are targeted to specific diseases and patient populations.

某些生物标志物（无论是基于遗传的还是蛋白质）可能表明一种类型的疗法或组合在某些患者中与其他患者相比会更好。

“我们的研究方案充满了探索性生物标志物工作，旨在了解哪些患者可能会从某些疗法中受益。我们致力于开发计划中的精确医学方法，我希望我们在未来几年中可能会看到巨大的进步。”格罗斯菲尔德说。

Grossfeld believes that a focus on precision medicine, as well as a strategic approach to building on existing therapies with investigational agents, have positionedBristol Myers Squibbat the forefront of immuno-oncology research. Despite advances in treatment of cancer with immunotherapy, a large number of unmet clinical needs remain. The goal is always to move the needle for patients.