From November 14 to 17, 2024, the Cellular Therapy and Immunotherapy Conference (CTI) was held in Hangzhou, China, bringing together global experts, scholars, and industry leaders in cellular and immunotherapy. The conference provided a vital platform for academic exchange and showcased cutting-edge advancements driving the field forward.During the event, Hematology Frontier had the privilege of interviewing Dr. Edmund K. Waller, Director of the Hematology and Bone Marrow Transplant Center at Emory University, USA. Professor Waller shared insights into the critical role of cellular and immunotherapy in cancer treatment and discussed the discovery and development of a novel immune checkpoint pathway mediated by the small neuropeptide VIP. Below is a summary of his key insights.Key Highlights
- New Hope for Resistant Cancers: Cellular and immunotherapy, as a new pillar of cancer treatment, offers hope for patients unresponsive to chemotherapy by effectively overcoming drug resistance and precisely targeting cancer cells.
- Discovery of VIP Pathway: A novel immune checkpoint pathway mediated by the neuropeptide VIP (vasoactive intestinal peptide) has been identified. VIP suppresses T-cell activity against cancer cells, but the application of specific antagonists can restore T-cell functionality.
- Promising Preclinical Results: In mouse models of leukemia and pancreatic cancer, a long-acting peptide antagonist targeting the VIP pathway demonstrated significant efficacy, requiring only weekly administration.
- Combination Therapy Potential: VIP antagonists can be combined with other immune checkpoint inhibitors or low-dose chemotherapy to enhance T-cell responses against cancer, offering a new strategy for cancer treatment.
Q1: Could you briefly introduce the current research landscape in cancer immunotherapy, particularly in novel immune checkpoint pathways, and why you chose this area as your focus?
Dr. Edmund K. Waller: It’s an honor to be here in Hangzhou and participate in this Cellular Therapy and Immunotherapy Conference. As an oncologist, I often treat patients whose cancer progresses despite standard chemotherapy. Cellular and immunotherapy represent the fourth pillar of cancer treatment, alongside surgery, radiation, and chemotherapy.
Immunotherapy is especially promising for patients who fail earlier treatments. It can overcome cancer cell resistance to chemotherapy and target cancer cells wherever they are in the body, offering a new level of precision. This unique mechanism gives immunotherapy enormous therapeutic potential and provides hope for patients who otherwise have limited options.
Q2: How does the novel VIP-mediated immune checkpoint pathway compare to well-known pathways like CTLA-4 and PD-1? Does it offer greater therapeutic potential for cancer patients?
Dr. Edmund K. Waller: We’ve identified a novel immune checkpoint pathway mediated by a small neuropeptide called VIP (vasoactive intestinal peptide). VIP plays a critical role in regulating physiological functions like digestion, sleep, and blood pressure. However, it also exhibits immunosuppressive properties.
When VIP interacts with immune cells—especially cancer cells that overexpress VIP—it significantly weakens the ability of nearby T cells to attack those cancer cells. By using specific antagonists to block this pathway, we can reinvigorate T-cell activity, restoring their ability to destroy cancer.
In preclinical studies using mouse models of leukemia and pancreatic cancer, we’ve seen highly promising results. Building on this, we’ve developed a long-acting peptide antagonist that only needs to be administered once a week, greatly improving treatment convenience.
This VIP antagonist shows potential to complement existing immune checkpoint therapies targeting pathways like PD-1, TIM-3, or LAG-3. Moreover, it can be combined with low-dose chemotherapy to further enhance T-cell responses against cancer. These combinations open new therapeutic possibilities for patients and pave the way for more effective treatment strategies.
Q3: What challenges have you encountered in researching this novel immune checkpoint pathway, and how have you overcome them?
Dr. Edmund K. Waller: When we first began exploring this field, there were no effective VIP receptor antagonists available. We spent considerable time and effort screening various peptide sequences and designing a more potent receptor antagonist.
The second challenge was the short half-life of peptides, which limited their therapeutic utility. To address this, we innovatively coupled the peptide to the immunoglobulin heavy chain region, enabling a weekly dosing regimen.
The third challenge lies in advancing to clinical trials, which requires extensive toxicology and pharmacokinetics studies in animal models. Fortunately, we’ve made significant progress thanks to funding support from the US federal government through the Small Business Innovation Research (SBIR) program. Additionally, we co-founded Cambium Oncology, a company dedicated to supporting this research and raising the necessary resources to move the project forward.
Conclusion
Dr. Edmund K. Waller’s groundbreaking work highlights the potential of VIP-mediated immune checkpoint pathways and their antagonists in cancer treatment. By blocking the interaction between VIP and immune cells, his team has successfully restored T-cell functionality, offering a new avenue for combating cancer.
The development of a long-acting peptide antagonist that requires only weekly administration marks a significant step forward in improving treatment accessibility and patient convenience. Despite facing challenges, Professor Waller’s team has made remarkable progress, supported by SBIR grants and collaborative efforts through Cambium Oncology.
As this research advances toward clinical application, we eagerly anticipate further breakthroughs that could revolutionize cancer treatment and bring renewed hope to patients worldwide.
About Dr. Edmund K. Waller
- Director of the Hematology and Bone Marrow Transplant Center, Emory University
- Renowned oncologist with extensive expertise in cellular and immunotherapy
- Leading researcher in novel immune checkpoint pathways and T-cell immunotherapy
- Co-founder of Cambium Oncology, focused on developing innovative cancer therapies
