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Drug intelligence / Profile preview
Combotox
- Development stage
- Phase 1
- Lead developer
- UT Southwestern Medical Center
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics, Recombinant Proteins and Enzymes
- Administration
- Intravenous
01
Overview
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.
- Brand names
- Combotox
- Other names
- anti-CD19-dgRTA + anti-CD22-dgRTAHD37-dgRTA + RFB4-dgRTAanti-CD19-dgRTA and anti-CD22-dgRTA immunotoxin cocktailanti-CD-19-dgRTA and anti-CD22-dgRTA immunotoxin cocktailanti-CD 19-dgRTA and anti-CD22-dgRTA immunotoxin cocktail
02
Targets
60S (Eukaryotic 60S ribosomal subunit)CD19 (B lymphocyte antigen CD19)CD22 (Cluster of Differentiation 22)
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