Therapeutic antibodies: successes, limitations and hopes for the future

Abstract

With more than 20 molecules in clinical use, monoclonal antibodies have finally come of age as therapeutics, generating a market value of $11 billion in 2004, expected to reach $26 billion by 2010. While delivering interesting results in the treatment of several major diseases including autoimmune, cardiovascular and infectious diseases, cancer and inflammation, clinical trials and research are generating a wealth of useful information, for instance about associations of clinical responses with Fc receptor polymorphisms and the infiltration and recruitment of effector cells into targeted tissues. Some functional limitations of therapeutic antibodies have come to light such as inadequate pharmacokinetics and tissue accessibility as well as impaired interactions with the immune system, and these deficiencies point to areas where additional research is needed. This review aims at giving an overview of the current state of the art and describes the most promising avenues that are being followed to create the next generation of antibody-based therapeutic agents.

Figure 1

Chimeric and humanized antibodies. Murine sequences are depicted in red and human sequences in green, using light colours for light chain and dark colours for heavy chains.

Figure 2

Antibody fragments with therapeutic potential. A conventional antibody is depicted in green (light for light chain, dark for heavy chain, blue triangle indicate the glycosylation site) and the derived fragments (shaded areas represent the binding sites). The orange colour symbolizes a different specificity. HcAb from camelids and their fragments (sdAb for single-domain antibodies) are depicted in mauve or blue. The red molecule represents a cytokine or a toxin. bsAb, bispecific antibodies; bsFab, bispecific Fab fragment; HcAb, heavy chain only antibodies.