Researchers at the University of Pittsburgh have made a notable advance in cancer immunotherapy by testing tebotelimab, a monoclonal antibody designed to engage the immune system against tumors in two complementary ways. In a study involving 269 patients whose cancers had not responded to prior treatments, 34% showed a reduction in tumor size after receiving this dual-action therapy. The findings appear in Nature Medicine as part of ongoing efforts to broaden the reach of immune-based cancer treatments.
One central role of the immune system is to monitor and eliminate abnormal cells that arise during the body’s daily cycles. Tumors often develop strategies to dodge this surveillance, which has driven the rise of immunotherapy as a major treatment frontier. By targeting checkpoints that tumors exploit, therapies can unleash immune responses that were previously blocked. Tebotelimab works by inhibiting two checkpoint proteins, PD-1 and LAG-3, with the goal of sustaining immune activity against cancer cells.
In the trial sponsored by MacroGenics, the company developing tebotelimab, investigators enrolled 269 cancer patients who had seen limited benefit from other options. Tumor types included ovarian, breast, head and neck, cervical cancers, and lymphomas. Following treatment with tebotelimab, measurable tumor shrinkage occurred in about one third of participants, signaling meaningful clinical activity across diverse cancer settings.
Another phase of the study expanded to 84 patients with advanced HER2-positive cancers who were treated with a combination of tebotelimab and margetuximab, an approved agent for this tumor subtype. The observed response rate of 19% in this group is notable given that prior responses for these patients were nearly absent. Authors emphasize that the dual drug approach may offer an added advantage in this difficult-to-treat area, aligning with the broader goal of stacking immune triggers to intensify anti-tumor effects.
Evidence from the researchers indicates that tebotelimab may more efficiently block both PD-1 and LAG-3 compared with using two separate medications. When two separate drugs are used, they can end up binding to distinct immune cells, with some cells blocked only for PD-1 and others only for LAG-3. Tebotelimab binds to and inhibits both targets at once, potentially producing a more unified blockade of these immune checkpoints and enabling a coordinated attack on tumors.
Overall, the results support the potential of dual-checkpoint inhibition to broaden the applicability of immunotherapy across tumor types. As more patients gain access to treatments that reawaken the immune system, ongoing trials will determine where this dual approach fits within existing regimens and how it can be combined with other standard therapies to improve outcomes for people living with cancer.
Additional context from the study highlights the continued evolution of immune-based strategies, which seek to overcome resistance mechanisms and extend the benefits of immunotherapy to a wider population. The data lay a foundation for future research, including assessments of long-term survival, tolerability, and optimization of combination therapies that harness the body’s natural defenses to fight cancer more effectively.