Antibody targeted drugs as cancer therapeutics

Abstract

Treatment of cancer is a double-edged sword: it should be as aggressive as possible to completely destroy the tumour, but it is precisely this aggressiveness which often causes severe side effects - a reason why some promising therapeutics can not be applied systemically. In addition, therapeutics such as cytokines that physiologically function in a para- or autocrine fashion require a locally enhanced level to exert their effect appropriately. An elegant way to accumulate therapeutic agents at the tumour site is their conjugation/fusion to tumour-specific antibodies. Here, we discuss recent preclinical and clinical data for antibody-drug conjugates and fusion proteins with a special focus on drug components that exert their antitumour effects through normal biological processes.

Increasing the Antitumor Effect of an EpCAM-Targeting Fusion Toxin by Facile Click PEGylation

“…Recent advances in antibody engineering and linker technology, together with a growing arsenal of potent anticancer agents, have paved the way for the development of drug conjugates targeting tumors with exquisite efficacy and specificity (1)(2)(3). In theory, many different types of payloads can be linked to antibodies; in practice, however, engineering ADC with high stability and efficacy has been hampered by technical limitations and unfavorable properties inherent to the antibody format (3)(4)(5)(6).…”

“…Tumor targeting with naked antibodies and antibody drug conjugates (ADC) has become an established strategy for cancer-related therapy, particularly if conventional therapies have failed (1,2). Recent advances in antibody engineering and linker technology, together with a growing arsenal of potent anticancer agents, have paved the way for the development of drug conjugates targeting tumors with exquisite efficacy and specificity (1)(2)(3).…”

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

“…Monoclonal antibodies and their derivatives are increasingly being used in anticancer therapeutic strategies for the selective delivery of bioactive agents (e.g., full immunoglobulins for Fc-mediated cell killing, drugs with cleavable linkers, radionuclides, photosensitizers, pro-coagulant factors, cytokines) to the tumour environment, thus sparing normal tissues (Payne, 2003;Adams and Weiner, 2005;Neri and Bicknell, 2005;Carter, 2006;Schrama et al, 2006;Schliemann and Neri, 2007;Carter and Senter, 2008). Although originally monoclonal antibodies specific to membrane antigens on cancer cells have been used for tumour targeting applications, alternative targets such as markers of angiogenesis (Schnitzer, 1998;Thorpe, 2004;Neri and Bicknell, 2005), stromal antigens (Hofheinz et al, 2003;Rybak et al, 2007;Schliemann and Neri, 2007) and intracellular proteins released at sites of necrosis (Miller et al, 1993;Street et al, 2006) are increasingly being considered.…”

Les immunoconjugués, anticorps « armés » pour combattre le cancer

“…Les anticorps armés d'une drogue de chimiothérapie (antibody-drug conjugates ou ADC en anglais) composent, avec les radio-immunoconjugués et les immunotoxines, la classe d'agents thérapeutiques très prometteuse des immunoconjugués [1,2] (➜). Dans les trois cas, l'objectif est identique : il s'agit d'utiliser la spécificité d'un anticorps pour cibler la cellule tumorale et libérer à l'intérieur ou à proximité de celle-ci, un composé hautement toxique qui lui est couplé, comme un agent cytotoxique, un agent radioactif ou une toxine (Figure 1).…”