Lessons From Evolution: From Innate Immunity to Novel Cancer Immunotherapies

Author: Christopher Arendt, PhD, Head, Oncology Cell Therapy and Therapeutic Area Unit

Immunotherapies on the rise

In recent years, we’ve seen remarkable progress in combatting devastating cancers, with the rise of immunotherapies across a breadth of therapeutic modalities, from antibody-based immunomodulators to cell-based therapies, to other emerging technologies. And yet, while there are more than 30 approved immunotherapies on the market today, a minority of patients respond to these available treatments, demonstrating a necessity for more effective and tolerable options.1

In light of our ultimate goal of offering curative-potential therapies to as many people living with cancer as possible, we now have the opportunity to build upon these successes by leveraging our ever-expanding insights into new mechanisms of action at the level of the immune system to advance standards of care.

Leading the way: Immunotherapies leveraging adaptive immunity

Today’s immunotherapies specifically engage adaptive immunity, an arm of immunity that forms the basis for our modern approach to vaccination. In the field of cancer therapies, adaptive immune mechanisms focus on T lymphocytes, a cavalry of highly specialized cells that individually possess unique receptors to seek out and destroy “abnormal” cells, specifically those with mutations linked to tumor progression.

Immune checkpoint inhibitors are designed to augment anti-tumoral T cell responses, while chimeric antigen receptor (CAR)-T cell therapies are predicated on a “synthetic biology” approach, in which a large swath of the T cell army is engineered to mediate an attack in response to a specific tumor-associated antigen, such as CD19 or B-cell maturation antigen (BCMA).

Just as these T cell-focused immunotherapies have illuminated the incredible potential of the immune system’s “firepower” in combating tumors, they have also provided insights into further trickery exploited by cancers to gain an upper hand.

New paradigms: The potential of innate immunity

As we look toward new mechanisms of action to address resistance and relapse to current immunotherapies, there is compelling rationale for broadening our purview outside of the adaptive immune system.

From the day we are born, the innate immune system serves as the body’s first defense mechanism against disease. Innate immunity has evolved to respond to a wide breadth of insults, with the power to orchestrate a broad arsenal of immune cell types and mechanisms that help to fend off infections or, potentially, cancers. Unlike adaptive immunity, innate immunity provides immediate and broad immune responses to these threats, offering a quicker immune attack and access to a wide array of mechanisms to promote disease resolution. Novel and emerging approaches that leverage innate immunity may have the ability to transform the current state of cancer care in meaningful ways. By harnessing the untapped power of the innate immune system to attack cancer, we may be able to overcome the limitations of current immunotherapies through additional mechanisms and tools that evolution has made available for therapeutic modulation.

Looking ahead

At Takeda Oncology, our commitment to science, collaboration and innovation includes a robust pipeline, composed of first-in-class mechanisms of action designed to harness the power of innate immunity to broaden the impact of immunotherapies. We’ve extended our scope to investigate innate immunity enhancers and innate immune cell platforms, in addition to tumor-selective cell engagers and tumor micro-environment disrupters designed to further expand our armory to affect meaningful benefit for patients.

While we acknowledge that cancer is clever, we are inspired by the conviction that “science is smarter.”  Driven to make a difference for patients who are waiting, researchers around the globe, including those at Takeda, are uncovering new insights into cancer’s weaknesses. This momentum cannot slow down; we owe it to patients to partner and invest wisely, and to advance with urgency the most promising opportunities to outsmart cancer and transform current standards of care.

Learn more about Takeda’s pipeline here.

 

References

1 Johns Hopkins Medicine. Immunotherapy: Precision Medicine in Action. https://www.hopkinsmedicine.org/inhealth/about-us/immunotherapy-precision-medicine-action-policy-brief.html. Accessed October 7, 2021.