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Combotox is an investigational immunotoxin cocktail comprising a 1:1 mixture of two monoclonal antibodies, HD37 (targeting CD19) and RFB4 (targeting CD22), each chemically conjugated to a deglycosylated ricin A chain (dgRTA). Developed primarily for B-cell malignancies, particularly precursor B-lineage acute lymphoblastic leukemia (ALL), Combotox utilizes the dual-specificity of its antibodies to bind and internalize into malignant B-cells. Once internalized, the ricin A chain payload enzymatically inactivates the 60S ribosomal subunit by cleaving a specific adenine residue from the 28S ribosomal RNA, thereby halting protein synthesis and inducing apoptosis. This dual-targeting approach is designed to increase efficacy and prevent tumor escape due to antigen heterogeneity. Combotox has been evaluated in Phase I clinical trials for both pediatric and adult patients with relapsed or refractory B-lineage ALL.
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