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Anti-CD22 Onconase: preparation and characterization
Dianne L Newton1, Luke H Stockwin, Susanna M Rybak
1NCI-Frederick, National Institutes of Health, Frederick, MD, USA.
Abstract:
Antibodies can be conjugated to effector molecules to derive targeted therapeutics with properties such as cell-specific cytotoxicity. The murine anti-CD22 antibody RFB4 linked to a member of the ribonuclease A superfamily, Onconase (Onc), becomes a potential drug candidate for non-Hodgkin's lymphoma. Onc is currently in Phase III clinical trials for unresectable malignant mesothelioma but conjugation to RFB4 considerably enhances its specificity for CD22+ lymphomas. RFB4-targeted Onc is effective in preclinical models, causes little non-specific toxicities in mice, and has favorable formulation properties. Derivatization and conjugation of RFB4 and Onc have been optimized.
Insights
A novel antibody-drug conjugate, RFB4-Onconase, targets CD22+ lymphomas. This targeted therapy shows efficacy in preclinical models with low toxicity, offering a promising treatment for non-Hodgkin
Area of Science:
- Oncology
- Immunotherapy
- Biochemistry
Background:
- Antibody-drug conjugates (ADCs) offer targeted delivery of cytotoxic agents.
- Non-Hodgkin's lymphoma (NHL) expresses the CD22 antigen.
- Onconase (Onc) is a ribonuclease with cytotoxic potential.
Purpose of the Study:
- To develop a targeted therapeutic for CD22-expressing lymphomas.
- To evaluate the efficacy and safety of RFB4-conjugated Onconase (RFB4-Onc).
Main Methods:
- Conjugation of the anti-CD22 antibody RFB4 to Onconase.
- Preclinical testing in lymphoma models.
- Assessment of specificity and toxicity.
Main Results:
- RFB4-Onc demonstrated enhanced specificity for CD22+ lymphomas.
- Effective cytotoxicity was observed in preclinical models.
- Minimal non-specific toxicities were noted in murine studies.
Conclusions:
- RFB4-Onc is a potential drug candidate for non-Hodgkin's lymphoma.
- Optimized derivatization and conjugation enhance therapeutic potential.
- Targeted delivery of Onconase via RFB4 improves specificity and reduces toxicity.
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