The state of cancer treatment


Aiman Shalabi, Ph.D

Immune-mediated therapy for cancer —or IMT-C—is a new, promising therapeutic approach that leverages the power of the immune system to fight cancer. In essence, by targeting the immune system, these agents may lead to durable and prolonged response rates across a range of cancer types.
Aiman Shalabi, Global Product Vice President, Oncology talks more about the importance of IMT-C, and why the biologics organization has made this one of the focal points of its oncology program.

What makes IMT-C so important in the repertoire of oncology treatment?
Anyone involved in oncology understands the limitations of existing treatments. Tumors are heterogeneous in that there are many different cells that often mutate and grow in different ways. In lung cancer, for example, there may be more than 60 different mutations. The challenge is that cancer often manages to continue replicating, and becomes resistant and returns to growth. This happens despite chemotherapy, surgery and other targeted therapies. Even worse, some of the existing therapies—especially chemotherapy—actually diminish the immune response, thus limiting the body’s own natural defense mechanisms to fight tumors.

Leveraging the power of the immune system, and specifically a human T-cell, is a fundamental change to the way we are treating cancer. This is because a T-cell identifies foreign objects and, once engaged, can inject potent and destructive chemicals directly into tumors.

We know from recent discoveries that tumors can hide from the immune system. They do this by generating a protective barrier on their surface that makes them invisible to the body’s natural fighting abilities. So, when a T-cell approaches a tumor, it’s turned “off” when the tumor protective barrier is there. When we remove a tumor specimen, for example, we often find inactive immune cells—basically cells that tried to kill the tumor but were exhausted and died.

What IMT-C does is threefold: (1) activates T-cells, the natural cells in the body that kill foreign objects—they need to be activated to work; (2) increases the number of T-cells, creating a larger army to fight tumors; and (3) removes the invisible shield that tumors create to protect themselves from an immune attack. The IMT-C agents empower the immune system—it’s a different way of looking at cancer treatment.

Practically speaking, how does this work?
We’re studying human monoclonal antibodies (mAbs) right now that focus on multiple approaches to leveraging the immune system. One of the most promising works by removing the invisible shield around tumors, which then allows the tumor to be recognized by the immune system. This invisible shield is a protein called programmed cell death ligand 1—or PD-L1. We are now able to block PD-L1 and remove it from the surface of tumors. Ultimately, this could give the immune system the ammunition it needs to counteract a tumor’s evasive maneuvers.

We’ve been hearing a lot about IMT-C combinations. What are these and how do they work?
Essentially, these are exactly what they suggest—different combinations of compounds—used either in conjunction with other immune-mediated therapy, other biologics or with small molecule compounds, and even radiation therapy—to attack the tumor from multiple different directions, giving it a one- two- or even three- punch attack at the same time.

Cancer biology is enormously complex, but these combination therapies have significant potential to empower the immune system to revert to its pre-cancer state.

What challenges do you see in getting IMT-C to the bedside?
The immune system isn’t always the first thing that comes to mind when we bring up cancer—including for clinicians whose treatment arsenal has been limited to traditional therapies. For a long time, the only tumors considered to have an immune component were kidney and skin cancers. We’re moving swiftly beyond that initial conventional wisdom, though still in the earlier stages of research. The early investigational results using IMT-C for lung cancer, for example, have been encouraging.

What’s important is that we’re committed to expanding our research in IMT-C because we believe that this is the future of cancer therapy—in fact, this is a cornerstone of our oncology portfolio. With our current clinical stage programs and a robust pre-clinical pipeline, we’re building one of the most comprehensive programs in immune-mediated therapy for cancer. We are also building an infrastructure and team solely dedicated to delivering this new generation of immunotherapies for late-phase development into the marketplace. We are focused on delivering an innovative solution to treating cancer. We hope—and our goal is—to bring this to patients as quickly as possible.