The Growing Challenge of Lung Cancer in the UAE and Beyond
Lung cancer continues to be one of the most formidable adversaries in oncology, claiming more lives globally than any other cancer type. According to recent estimates, it accounts for approximately 1.8 million deaths annually worldwide, with non-small cell lung cancer (NSCLC, representing 85% of cases) and small cell lung cancer (SCLC) posing distinct therapeutic hurdles. In the United Arab Emirates (UAE), lung cancer ranks as the third leading cause of cancer-related mortality and sixth in incidence, affecting both residents and expatriates amid rising smoking rates, air pollution, and an aging population. The age-standardized incidence rate hovers around 10-15 per 100,000, with projections indicating a significant uptick by 2030 due to lifestyle factors and delayed diagnoses. Early detection remains critical, as stage I diagnosis offers up to 70% five-year survival, plummeting to under 10% at advanced stages.
The UAE's National Cancer Control Plan, emphasizing screening and multidisciplinary care, aligns with global efforts like the WHO's initiatives. Yet, advanced cases demand innovative treatments beyond chemotherapy and checkpoint inhibitors like PD-1/PD-L1 blockers, which benefit only 20-40% of patients long-term. Enter next-generation immune cell therapies—chimeric antigen receptor T cells (CAR-T), CAR-natural killer (CAR-NK) cells, and tumor-infiltrating lymphocytes (TIL)—offering hope for durable responses in refractory disease.
From Checkpoint Inhibitors to Adoptive Cell Therapies
Immunotherapy has revolutionized lung cancer care since pembrolizumab's approval in 2015 for high PD-L1 NSCLC. These drugs unleash T cells against tumors but falter against 'cold' microenvironments lacking infiltration or antigen presentation. Adoptive cell therapies address this by engineering or expanding immune effectors for direct tumor lysis.
CAR-T therapy, FDA-approved for blood cancers, modifies patient T cells ex vivo with chimeric antigen receptors (CARs)—fusion proteins of antigen-binding domains, transmembrane hinges, costimulatory signals (e.g., CD28/4-1BB), and CD3ζ for activation. Upon reinfusion, CAR-T cells proliferate and persist, targeting surface antigens like mesothelin (MSLN) or EGFR variants overexpressed in 90% of NSCLC.
Similarly, CAR-NK cells use natural killer cells, abundant and MHC-independent, for 'off-the-shelf' scalability. TIL therapy expands tumor-resident T cells, capturing neoantigen-specific clones for polyclonal attack. These approaches bypass resistance mechanisms, with preclinical data showing tumor regression in lung models resistant to checkpoints.
CAR-T Cells: Precision Engineering Meets Lung Cancer
CAR-T targets in lung cancer include MSLN (upregulated in 70-90% NSCLC), HER2, ROR1, and DLL3 (SCLC-specific). Early trials faced cytokine release syndrome (CRS) and neurotoxicity from systemic delivery, but regional intrapleural administration mitigated this. In NCT02414269 (MSLN CAR-T), patients achieved median overall survival (OS) of 23.9 months, 1-year OS 83%, with stable disease in multiple cases.
- Intrapleural CAR-T enhanced persistence and reduced on-target off-tumor toxicity.
- Armored CAR-T secreting IL-12/IL-18 remodels immunosuppressive tumor microenvironments (TME).
- Multi-antigen CARs (e.g., EGFRvIII + IL13Rα2) combat heterogeneity and escape.
Logic-gated 'AND' CARs activate only on dual antigens, boosting specificity. Allogeneic platforms from iPSCs promise scalability, crucial for solid tumors.
CAR-NK Cells: Safer, Scalable Sentinels
Natural killer (NK) cells excel against MHC-low tumors via ADCC and NKG2D ligands. CAR-NK evades graft-vs-host disease, with shorter persistence offset by cytokine armoring. Preclinical DLL3-CAR NK-92 regressed SCLC xenografts; cytokine-induced memory-like (CIML) NK showed superior cytotoxicity against cancer stem cells (CSCs).
A Phase II trial reported 1-year progression-free survival (PFS) of 67% vs. 33% control. iPSC-derived CAR-NK, engineered for high-affinity CD16 and PD-1 knockout, are entering trials, positioning NK as ideal for UAE's diverse population needing rapid therapy.
TIL Therapy: Unleashing Endogenous Warriors
TILs, extracted from resected tumors, are expanded with IL-2, capturing neoantigen-reactive clones. Unlike CARs, TILs offer broad-spectrum recognition without antigen engineering. In NSCLC, CD39-CD73- stem-like TILs predict response. NCT03215810 (Phase I) yielded ~20% objective response rate (ORR), durable >1.5 years post-lymphodepletion.
- No CRS/neurotoxicity observed.
- Enriched neoantigen-reactive subsets enhance precision.
- Feasible for ICI-resistant patients.
IOV-LUN-202 (Phase II) confirms >20% ORR, aligning with melanoma success (FDA-approved lifileucel).
MBRU Dubai: At the Forefront of UAE Innovation
Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU) in Dubai exemplifies UAE's research ascent. Amina Mujahid, from MBRU's College of Medicine and Dubai Health, co-authored the seminal March 2026 Frontiers review synthesizing CAR-T/NK/TIL advances. This work underscores MBRU's role in translational oncology, supported by its Biomedical Research Center and ties to Dubai Health.
MBRU's prior studies on microgravity's impact on lung cancer immunity highlight microenvironment modulation. Amid UAE's National Guideline for Lung Cancer Screening (launched Nov 2025), MBRU drives from bench to bedside.
Clinical Trials Lighting the Path Forward
Over 70 studies (2015-2025) inform progress. Key CAR-T: NCT03525782 (MUC1, stable disease 11/20); NCT03392064 (DLL3, partial response). NK: enhanced PFS in combinations. TIL: durable responses in advanced NSCLC. UAE trials via Dubai Health integrate these, aligning with GCC collaborations.
| Therapy | Key Trial | Outcome |
|---|---|---|
| CAR-T (MSLN) | NCT02414269 | Median OS 23.9 mo |
| CAR-NK (DLL3) | Preclinical | Tumor regression |
| TIL | NCT03215810 | 20% ORR |
Navigating Challenges: Antigen Escape and TME
Solid tumors resist via heterogeneity (e.g., EGFR loss), TME suppression (TGF-β, MDSCs), poor trafficking. Solutions: multi-antigen CARs, armored cells (IL-15 for persistence), regional delivery, combos with ICIs/radiotherapy. Manufacturing scalability via allogeneic NK/TIL addresses cost/access in UAE.
UAE's Strategic Vision and Global Impact
UAE's Cancer Control Plan targets 18% mortality reduction by 2025, investing in immunotherapy via MBRU, Khalifa University. Partnerships like TII-Burjeel advance CAR-T. Future: biomarkers, AI-optimized trials, equitable access.
For researchers/students, MBRU offers cutting-edge programs. Patients gain hope from these UAE-led innovations.
Photo by Robina Weermeijer on Unsplash
Actionable Insights for Stakeholders
- Clinicians: Consider trials for refractory cases.
- Researchers: Focus multi-modal engineering.
- Patients: Advocate screening per MoHAP guidelines.
- Policymakers: Fund scalable NK/TIL platforms.
These therapies herald a new era, with MBRU exemplifying UAE's oncology leadership.
