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Evolution of the therapeutic use of new monoclonal antibodies
M I Colnaghi1, S Ménard, S Canevari
1Division of Experimental Oncology E, Istituto Nazionale Tumori, Milan, Italy.
Abstract:
Peptide or carbohydrate epitopes resulting from aberrant glycosylation, receptors for growth, and differentiation signals have recently been reexamined as candidates for monoclonal antibody-guided therapy. Microdistribution studies have demonstrated the limited penetration of radiolabeled antibodies in tumors. Increased tumor capillary permeability has been obtained by pretreatment with cytokines or by exploitation of monoclonal antibodies against tumor endothelial cells. The use of monoclonal antibodies for combined therapies based on different rationales (multiple monoclonal antibodies, monoclonal antibodies plus cytokines, and monoclonal antibodies plus drugs) is a recent development, and the retargeting of effector cells using hybrid monoclonal antibodies can be considered an extension of this approach. A major driving force in the field of immunotoxins today is represented by progress in protein engineering. Genes encoding various toxins have been cloned, and novel molecules with more desirable biologic properties have been produced. Also, genetic engineering techniques help in overcoming the major limitation in the clinical use of rodent monoclonal antibodies, ie, human antiimmunoglobulin response.
Insights
Monoclonal antibodies targeting aberrant glycosylation show promise for cancer therapy. Advances in protein engineering enhance immunotoxin development and overcome immune responses to rodent antibodies.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Aberrant glycosylation epitopes and growth factor receptors are re-emerging targets for monoclonal antibody (mAb)-guided cancer therapy.
- Limited penetration of radiolabeled mAbs into tumors is a significant challenge.
- Strategies to enhance tumor capillary permeability include cytokine pretreatment or targeting tumor endothelial cells with mAbs.
Purpose of the Study:
- To explore novel therapeutic strategies using monoclonal antibodies for cancer treatment.
- To investigate the potential of combined immunotherapies and advancements in immunotoxin development.
- To address limitations in the clinical application of rodent monoclonal antibodies.
Main Methods:
- Re-examination of peptide/carbohydrate epitopes from aberrant glycosylation and growth factor receptors as mAb targets.
- Utilizing cytokines or anti-tumor endothelial cell mAbs to increase tumor capillary permeability.
- Developing combined therapies: multiple mAbs, mAbs plus cytokines, mAbs plus drugs.
- Employing protein engineering and genetic engineering for immunotoxin development and overcoming anti-immunoglobulin responses.
Main Results:
- Demonstrated limited penetration of radiolabeled antibodies in tumors.
- Showed increased tumor capillary permeability through specific pre-treatments.
- Highlighted the development of combined immunotherapies and engineered immunotoxins.
- Addressed the human anti-immunoglobulin response limitation for rodent mAbs.
Conclusions:
- Monoclonal antibodies targeting specific epitopes and enhancing tumor penetration represent a promising therapeutic avenue.
- Combined immunotherapies and advanced immunotoxins offer new strategies for cancer treatment.
- Protein and genetic engineering are crucial for overcoming current limitations in antibody-based therapies.