Could the Bio Revolution Restore Balance to Immune Systems That Turn Against Our Bodies?
Written by Jürgen Eckhardt, Head of Leaps by Bayer
The human immune system is one of the greatest marvels of the biological world. An army of specialized cells works together to patrol our bodies in search of viruses, bacteria, and other invaders. Our immune systems can protect us against previously encountered pathogens — and even root out threats from within by finding and destroying cancerous cells. As the COVID pandemic has made clear, therapeutics like vaccines and immunotherapies that ignite our body’s powerful defenses are crucial tools in fighting disease.
But the immense power of the immune system can be a double-edged sword. Our immune cells communicate through complex molecular signals and feedback loops, and when these controls go awry, immune cells can start attacking the body’s own tissues. The darker side of immunity was long underappreciated by the medical community and only started gaining widespread recognition in the 1940s. But the importance of autoimmunity has gained attention in recent years, particularly with the suspected role of immune overdrive in long COVID.
More broadly, misdirected and overactive immune responses are now recognized as the causes of both chronic inflammation and a broad array of autoimmune diseases. An estimated 8% of the population is affected by these chronic, painful conditions, which include diseases as varied as type 1 diabetes, rheumatoid arthritis, Crohn’s disease, inflammatory bowel disease, and multiple sclerosis. For patients with autoimmune disease, treatment options have long been limited. Most therapies use immunosuppressants to dial back the immune system — but often with the side effect of weakening patients’ protections against other harmful diseases.
What if we could fine-tune the body’s immune responses to prevent inflammation and autoimmunity while leaving the rest of our immune protections intact? The Bio Revolution has brought an array of powerful, precise tools for engineering biology, ushering in an era of new therapeutic possibilities for these currently incurable autoimmune diseases. In recognition of this paradigm-shifting potential, we have designated autoimmunity as the focus of Leap 06 / Reverse autoimmune diseases and chronic inflammation.
Three recent investments highlight the thrilling potential of new technologies to change the landscape of autoimmune therapeutics, offering nuanced approaches that stand beside portfolio companies including Azitra and Edifice. The immune system has layers of cellular controls and feedbacks, and Mozart Therapeutics is designing therapies that target CD8 T regulatory cells, crucial controllers of the immune response. CD8 T regulatory cells ordinarily help detect, recognize, and eliminate overactive immune cells, making them natural partners in the quest to restore balance to the immune system. By building on and modulating the natural properties of these powerful cells, Mozart aims to tackle the root causes of autoimmune and inflammatory diseases to restore health to affected patients.
The complexity of the immune system is reflected in the diversity of autoimmune diseases, and the many complementary approaches are necessary to tackle them. Deka Biosciences is exploring the therapeutic potential of cytokines, a family of cellular messengers that help activate immune responses. Cytokines can have powerful effects in fighting cancer and modulating autoimmunity, but getting the right balance of cytokines to the right place is crucial for building an effective therapy. Deka has designed a protein platform that delivers combinations of cytokines directly to affected tissues or tumor environments, an approach that allows the therapy to be precisely controlled. What’s more, since patients often respond differently to cytokine therapies, Deka has developed tests for patients with cancer and inflammatory diseases to determine which of their therapies are most likely to be effective — a huge step towards precision medicine.
Yet another potential game-changing approach comes from GRO Biosciences, co-founded by pioneering synthetic biologist George Church. GRO aims to unlock the potential of protein therapies, a growing family of treatments that use proteins, Nature’s machines, to fight disease. In nature, proteins are made by stringing together building blocks from an alphabet of 20 amino acids, but GRO reprograms cellular machinery to expand this alphabet to include non-standard amino acids, opening new universes of possibility. These non-standard amino acids can be used to build protein therapies with better stability and potency than those made with natural amino acids alone. Moreover, this expanded protein alphabet makes it possible to engineer modified proteins that have fewer immunogenic side effects, broadening the application of these important therapies.
The immense complexity of the immune system is what allows it to fight disease — but when parts of this complex response go awry, the resulting inflammation and autoimmune diseases can be devastating. One silver lining is that this same complexity offers us multiple complementary opportunities to use our increasing understanding of immunity and the powerful new tools of the Bio Revolution to restore the balance between health and disease.