What question did this study set out to answer?

To evaluate the effectiveness of CBX-663, a TCR-mimetic T-cell engager, in solid tumor models targeting the TERT peptide-HLA complex.

CBX-663 Targets TERT Peptide-HLA Complex for Tumor Inhibition in Solid Malignancies

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This preclinical study shows that CBX-663 effectively inhibits tumors in solid malignancies, suggesting a new treatment avenue.

To evaluate the effectiveness of CBX-663, a TCR-mimetic T-cell engager, in solid tumor models targeting the TERT peptide-HLA complex.
Characterized CBX-663 in preclinical models of solid tumors.
Performed X-scan analysis to identify residues for TERT540 pHLA recognition.
Conducted a screen of over 6,000 human membrane proteins for off-target interactions.
Assessed cytokine release in HLA-A*02:01-positive PBMCs with and without tumor cells.
CBX-663 exhibited potent T-cell-mediated cytotoxicity against TERT- and HLA-A*02:01-positive tumor cell lines.
Achieved significant tumor control in NSCLC models in humanized mouse models.
Induced moderate cytokine release without off-target activity against unrelated HLA alleles or normal primary cells.
Repeat dosing was well tolerated with minimal adverse cytokine release.

Huang et al. (2026) studied this question.

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