TRAB in Medical Context
TRAB stands for Trifunctional Antibody or T cell-Redirecting Antibody, a bispecific immunotherapy that simultaneously binds tumor cells, T-cells (via CD3), and accessory immune cells to induce tumor destruction. 1, 2
Mechanism of Action
TRAB represents a unique class of bispecific antibodies with three distinct binding capabilities:
- Tumor cell binding: Targets tumor-associated antigens (e.g., EpCAM, GD2, GPC3, HER2/neu) expressed on cancer cells 1, 2
- T-cell engagement: Binds CD3 on T-cells to redirect them toward tumor cells regardless of T-cell receptor specificity 1, 3
- Accessory cell activation: Engages Fcγ receptors (types I, IIa, and III) on natural killer cells, dendritic cells, and macrophages 2
Clinical Indications
TRAB therapy is indicated for specific malignancies where conventional treatments have failed:
- Peritoneal carcinomatosis from gastric, ovarian, or other EpCAM-positive epithelial tumors when standard therapy is unavailable or ineffective 3, 2
- Malignant ascites in patients with EpCAM-positive carcinomas (catumaxomab is EU-approved for this indication) 2
- Solid tumors expressing specific antigens like GPC3 (hepatocellular carcinoma), particularly in non-immunogenic tumors resistant to checkpoint inhibitors 1
- Neuroblastoma expressing GD2 antigen, especially in high-risk or relapsed cases 4
Therapeutic Effects
TRAB induces tumor destruction through multiple mechanisms:
- T-cell-mediated cytotoxicity: TCR-independent anti-cancer T-cell response leading to direct tumor cell lysis 1, 2
- Antibody-dependent cellular cytotoxicity (ADCC): Via activation of FcγR-positive accessory cells 2
- Phagocytosis: Through macrophage activation 2
- Long-lasting anti-tumor immunity: Induction of tumor-specific CD4+/CD8+ T-lymphocytes that persist beyond treatment 3, 4
Administration and Dosing
For peritoneal carcinomatosis and malignant ascites:
- Route: Intraperitoneal infusion 3, 2
- Dosing schedule: Four escalating doses administered on days 0,3,7, and 10 2
- EpCAM-targeting TRAB: 10,20,50, and 150 µg 2
- HER2/neu-targeting TRAB: 10,40, and 80 µg 3
Clinical Outcomes
Evidence demonstrates meaningful clinical responses:
- Peritoneal carcinomatosis: 5 of 9 patients achieved stable disease or partial regression with mean time to progression of 3.6 months and mean survival of 11.8 months 3
- Immune response: Significant increase in tumor-reactive CD4+/CD8+ T-lymphocytes in 56% of treated patients 3
- Solid tumors: Conversion of poorly inflamed tumor microenvironment to highly inflamed state, enabling immune-mediated tumor control 1
Important Considerations
Common pitfall: TRAB is NOT a tumor marker or diagnostic test—it is an active immunotherapy agent. 1, 2
Safety profile: Transient cytokine elevation occurs but is manageable and reversible, with no significant organ toxicity in preclinical studies 1
Combination strategies: TRAB efficacy may be enhanced when combined with:
- Anti-PD-1 checkpoint inhibitors for improved humoral immune response 4
- Whole cell tumor vaccination for enhanced endogenous anti-tumor immunity 4
- Irinotecan for chemotherapy-resistant osteosarcoma (though this represents trabectedin chemotherapy, not TRAB immunotherapy) 5
Target selection: Success requires tumor expression of the targeted antigen with sufficient tumor selectivity to avoid on-target off-tumor toxicity 1