Antibody-based therapeutics in oncology

Abstract

The recent clinical and commercial success of anticancer antibodies, such as rituximab (Rituxan) and trastuzumab (Herceptin) has created great interest in antibody-based therapeutics for hematopoietic malignancies and solid tumors. Given the likely lower toxicity for antibodies versus small molecules, the potential increase in efficacy by conjugation to radioisotopes and other cellular toxins and the ability to characterize the target with clinical laboratory diagnostics to improve the drug's clinical performance, it is anticipated that current and future antibody therapeutics will find substantial roles alone and in combination therapy strategies for the treatment of patients with cancer. It is also likely that conjugation strategies will add new radiolabeled and toxin-linked products to the market to complement the recent approvals of ibritumomab tiuxetan (Zevalin) and gemtuzumab ozogamycin (Mylotarg). However, although there are a large number of agents in both early and later stages of clinical development, only a handful will make it through regulatory approval and become successful products. This review considers the structure of anticancer therapeutic antibodies, the techniques used to reduce their antigenicity, factors that influence efficacy and toxicity, conjugation with isotopes and toxins and antibody target validation.

A lectin array-based methodology for the analysis of protein glycosylation

“…Over 150 biopharmaceuticals have now gained medical approval and several hundred are in the pipeline, most of which are produced in mammalian cell systems [46][47][48][49]. Monitoring and characterization of glycosylation at early stages of biopharmaceuticals development is a subject of intense efforts for improving the throughput and efficiency of glycoanalysis methods.…”

Characterization of a Proapoptotic Antiganglioside GM2 Monoclonal Antibody and Evaluation of Its Therapeutic Effect on Melanoma and Small Cell Lung Carcinoma Xenografts

“…Numerous mAbs have been used to treat cancers successfully in preclinical animal models, and to date, eight have been approved for therapeutic use in man, whereas >50 are currently undergoing evaluation in clinical trials (reviewed in refs. [2][3][4][5]. Based on this experience, there is a very strong rationale for continued development of new mAbs for immunotherapy.…”

A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent

“…Immunotherapy represents an effective strategy to fight cancer, mainly based on antibodies specifically directed to selected cancer cells (Trikha et al, 2002;Ross et al, 2003). Obstacles to full success of present-day immunotherapy include: (i) immune responses against non-human, or even humanised antibodies (Kuus-Reichel et al, 1994); (ii) the large size of antibodies, which hinders their diffusion into bulky tumours.…”