Researchers from Singapore's A*STAR Institute of Molecular and Cell Biology (IMCB) and biotechnology company Intra-ImmuSG have reported promising Phase II clinical trial results for PRL3-zumab, a novel humanized antibody therapy targeting treatment-resistant solid tumors. Published in Cell Reports Medicine, the multicenter trial demonstrated that PRL3-zumab safely delays disease progression in patients with advanced cancers that have proven refractory to conventional treatments.
Breakthrough Targeting Strategy
PRL3-zumab represents a paradigm shift in cancer immunotherapy by targeting PRL3, an intracellular enzyme highly expressed in approximately 80% of solid tumors yet undetectable in healthy tissues. Unlike traditional antibody therapies that target extracellular or cell surface proteins, PRL3-zumab exploits the transient expression of PRL3 on cancer cell surfaces—a previously underappreciated phenomenon.
This innovative approach enables the immune system to specifically identify and eliminate malignant cells through antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis mechanisms. The strategy circumvents the longstanding challenge of targeting "undruggable" intracellular oncoproteins, potentially opening new frontiers for antibody engineering and immunotherapy.
Clinical Trial Results
The Phase II trial enrolled 51 participants with various advanced-stage solid tumors refractory to standard treatments, including conventional immunotherapies. Patients treated with PRL3-zumab showed median progression-free survival substantially longer than historical controls. Notably, one patient with Stage IV gastric cancer achieved disease stabilization lasting over 13 months—a significant extension compared to the typical two-month progression seen with existing therapies in similar patient populations.
The trial employed an innovative Single Evaluable Patient Single Cohort (SEPSC) design, allowing for rigorous intra-patient comparisons by contrasting each patient's progression-free survival on PRL3-zumab against their own historical treatment responses and established benchmarks. This analytical approach enhanced the precision and validity of efficacy assessments in the heterogeneous patient population.
Safety Profile and Global Expansion
The trial reported no serious drug-related adverse events, demonstrating PRL3-zumab's favorable safety profile—a critical consideration for patients with limited treatment options who often face high toxicity burdens from conventional therapies. This tolerability supports the therapy's potential integration into existing treatment regimens.
Preliminary data from concurrent trials in Malaysia and China have revealed encouraging signs of tumor regression, suggesting PRL3-zumab may not only contain but actively reduce tumor burden. While final evaluations from these ongoing international studies are under analysis, initial findings indicate a broader efficacy spectrum across different populations and tumor types.
Scientific Foundation and Development
PRL3-zumab's development traces back to Professor Qi Zeng from ASTAR IMCB, who first identified PRL3 in 1998, uncovering its pivotal role in cancer metastasis and therapeutic resistance. His pioneering work illuminated PRL3 as a crucial driver of tumor aggressiveness, inspiring the targeted antibody approach that catalyzed the formation of Intra-ImmuSG, an ASTAR spin-off dedicated to translating laboratory discoveries into clinical innovations.
"PRL3-zumab represents a true bench-to-bedside success story. This research product has already benefited many late-stage cancer patients and offers new hope to those with rare, aggressive cancers, helping to extend both survival and quality of life in patients who had run out of options," said Professor Qi Zeng, Senior Principal Scientist at A*STAR IMCB and Founder and Chief Scientific Officer of Intra-ImmuSG.
Implications for Cancer Treatment
The success of PRL3-zumab challenges long-held assumptions about druggable targets in oncology. Historically, intracellular oncoproteins were considered inaccessible to antibody-based therapies due to their localization behind cell membranes. This breakthrough demonstrates that intracellular antigens, when transiently presented on cell surfaces, can be exploited therapeutically, potentially expanding the repertoire of actionable cancer targets.
The approach represents a transformation in cancer treatment philosophy—shifting from targeting surface markers alone to embracing the dynamic biology of tumor cells, including intracellular processes. This could lead to development of a new class of immunotherapies directed at intracellular pathways, providing hope for patients with rare, aggressive malignancies lacking effective treatment options.
Full data from ongoing Phase II studies across multiple Asian countries are anticipated to further elucidate PRL3-zumab's therapeutic potential, with researchers optimistic that these investigations will provide comprehensive evidence supporting regulatory approvals and clinical adoption.
