New Generation of Therapies Targets ‘Cold’ Solid Tumors
The oncology landscape is undergoing a significant transformation as researchers and biotechnology firms shift their focus toward “cold,” immunotherapy-resistant solid tumors. Historically, cancers such as prostate, pancreatic, and breast tumors have remained shielded from the breakthroughs seen in melanoma or lung cancer, largely due to their immunosuppressive microenvironments and low T-cell infiltration. However, 2026 has emerged as a landmark year, with high-stakes dealmaking and a wave of new clinical programs attempting to breach these biological defenses.
Among the most promising developments is the move toward natural killer (NK) cell engagers. On May 14, 2026, GT Biopharma, Inc. (NASDAQ: GTBP) announced the dosing of the first patient in a Phase 1 dose-escalation trial for GTB-5550, a B7-H3-targeted NK cell engager. The trial is designed to address the specific challenges of solid tumors, with an initial focus on identifying the maximum tolerated dose in prostate cancer patients—a group where the B7-H3 protein is expressed in over 90% of cases.
“Dosing the first patient in our GTB-5550 Phase 1 trial is a pivotal milestone for GT Biopharma and represents the natural evolution of our TriKE® platform into the broader opportunity of treating patients with a variety of solid tumors.”— Michael Breen, Executive Chairman and Chief Executive Officer, GT Biopharma, Inc.
The urgency to innovate is shared by the broader scientific community. While corporate efforts like GT Biopharma’s focus on innate immunity, independent research institutions are exploring diverse mechanisms to overcome tumor resistance. Recent breakthroughs published in Science by researchers at Columbia University highlight the potential of HLA-independent T-cell receptors (HITs), which have successfully cleared kidney, pancreatic, and ovarian solid tumors in mouse models. Similar progress is underway in Montreal, where institutions such as the Institut du cancer de Montréal are advancing cell therapies that reactivate anti-tumor immune cells, while other investigators are exploring magnetic navigation to deliver precision bacterial payloads to tumor sites.
These therapies represent a departure from traditional checkpoint inhibitors, which often fall short in “cold” environments. Instead, new programs are engineered to utilize tumor microenvironment activation and innate immune recruitment to bypass the MHC presentation issues that hinder current standards of care.
The current clinical landscape is characterized by:
- Rapid progression of NK cell programs aimed at historically untreatable solid disease.
- Expansion into basket trials, with GTB-5550 targeting up to seven distinct tumor types including bladder, lung, and ovarian cancers after initial dose escalation.
- Increased investment in diverse modalities, ranging from engineered T-cell receptors to bacteria-magnetism therapies.
As these therapies move into and through the clinic, they offer hope for patients facing advanced diseases that have defied conventional treatment for decades. With over $1.7 billion in recent sector dealmaking, the race to turn “cold” tumors “hot” has firmly established itself as the next great frontier in cancer care.
