Frontiers in Tumor Immunology

Frontiers in Tumor Immunology

The oncology landscape is undergoing a rapid and profound transformation, driven by remarkable progress in precision medicine, digital technologies, and immunotherapy. One of the main challenges is navigating the complexity of cancer biology, particularly for patients facing relapse or unresponsiveness to treatments. I firmly believe that our mission is not just keeping pace with these complexities of cancer biology but leading the way to solve problems that genuinely improve the lives of our patients.

At Merck KGaA, Darmstadt, Germany, I have the privilege of leading a dynamic group of 25 scientists. It’s their diverse backgrounds and cultures that fuel our creative problem-solving. Spanning across Massachusetts, USA and Darmstadt, Germany, we cultivate an open, respectful, and collaborative culture that continually drives us to pursue excellence. Together, we’re committed to crafting precision tools that will be the next generation of cancer therapies.

Targeting Cancer at Its Core

Our team's focus is to empower the body's immune system in the fight against cancer. We concentrate on two essential pillars: activating the immune response against cancer and fine-tuning T-cell activation. We’re building on the foundations of antibody-drug conjugate research and immune checkpoint therapies, with the goal of expanding the reach of cancer therapies to benefit a broader patient population.

One challenge with many immune-activating treatments is the potential for toxicity. To help address this, we draw insights from meticulously engineered antibody-drug conjugates (ADCs) designed to deliver and release cytotoxic payloads—types of small molecules that can cause cell damage or death—to the tumor. Through targeted toxin delivery, we can strike cancer at its core with the potential to reduce damage by decreasing the cytotoxic effect on healthy cells.

The Next-Generation of ADCs

The same principle of bringing treatments selectively to cancer cells can be used for immune-activating therapies. In close collaboration with the ADC team at Merck KGaA, Darmstadt, Germany, we are investigating the use of immune agonist ADCs. Instead of a toxic payload, these antibodies carry an immunostimulatory payload. Once internalized into the cancer cells and/or immune cells within tumors, immune agonist ADCs have the potential to amplify the immune system's activity against tumors.

Championing T cells

At the heart of our second pillar are T cells, the immune system’s elite guardians, capable of recognizing and attacking cancer cells. Here, we draw inspiration from the success of immune checkpoint inhibitors. Tumors can inhibit or put the ‘brakes’ on T cell activity, and checkpoint inhibitors—a groundbreaking form of immunotherapy—essentially release these brakes to re-awaken T cells.

This innovative therapy has revolutionized the oncology field by significantly advancing the treatment of certain aggressive cancers, and we continue to explore innovative methods of activating T cells. These include identifying T-cell targets, enhancing T-cells activation, and interfering with inhibitory pathways. Our strategy holds the potential to generate lasting responses and to extend lives by leveraging the immune system's memory. Importantly, it offers hope to patients who have not responded to current immunotherapies.

While T cells remain central to our research, we also investigate other critical immune cells, including dendritic cells and macrophages, which play essential roles in initiating the anti-tumor immune response. Additionally, we’re developing bispecific antibodies that direct immune activation exclusively toward the tumor, to further empower the immune system in its battle against cancer.

As we dive deeper into the field of cancer treatments, our focus on targeted therapies continues to evolve. Our dedication lies in solving real challenges and providing hope for patients who deserve a brighter future. By harnessing the immune system’s potential, we're helping to reshape the landscape of cancer treatment to make it more precise, effective, and hopeful. The journey is demanding, but with dedicated teams and a collaborative spirit, we’re moving closer to a world where cancer is no longer an unbeatable foe.

US-NONO-00617 06/2024