A Novel Dual-Payload ADC for the Treatment of HER2+ Breast and Colon Cancer

Antibody-drug conjugates (ADCs) have demonstrated a great therapeutic potential against cancer due to their target specificity and cytotoxicity. To exert maximum effect on cancerous cells, we conjugated two different payloads amino acids, cysteines (cys) lysines (lys), trastuzumab, which is humanised anti-HER2 monoclonal antibody. First, trastuzumab was with monomethyl auristatin E (MMAE), an antimitotic agent, through cleavable linker (Val-Cit) prepare ADC (Tmab-VcMMAE). Then, the (Tmab-VcMMAE) second Mertansine (DM1), via non-cleavable Succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) form dual conjugate (Tmab-VcMMAE-SMCC-DM1). Our results indicated that dual-payload conjugate, Tmab-VcMMAE-SMCC-DM1, had synergistic superior cytotoxic compared alone. Ultimately employing conjugation approach has overcome treatment-resistance tumour recurrences could pave way employ other construct (or multiple) payload complexes.