Drug Targeting Organ-Specific Strategies

1.2.2 Monoclonal Antibodies and Fragments
1.2 Carriers used in Drug Targeting 3
Figure 1.1. Schematic representation of four major liposome types. Conventional liposomes are either
neutral or negatively charged. Stealth liposomes are sterically stabilized and carry a polymer coating to
obtain a prolonged circulation time in the body. Immunoliposomes are antibody targeted liposomes and
can consist of either conventional or sterically stabilized liposomes. Positive charge on cationic
liposomes can be created in various ways. Reproduced from reference [112] with permission.
The development of monoclonal antibodies by Köhler and Milstein in 1975 paved the way to
antibody therapy for disease [5]. In the last 25 years, the number of pre-clinical and clinical
studies with monoclonal antibodies and derivatives thereof have greatly increased. The majority
of strategies based on antigen recognition by antibodies have been developed for cancer
therapy. These strategies are mostly aimed at tumour associated antigens being present
on normal cells but overexpressed by tumour cells [6]. More recently, antibodies against other
molecules have been developed for clinical application. Examples are anti-TNFα antibodies
for treatment of chronic inflammatory diseases and anti-VEGF (vascular endothelial
growth factor) antibodies which inhibit new blood vessel formation or angiogenesis.
The advent of recombinant DNA technology led to the development of antibodies and
fragments that are tailored for optimal behaviour in vivo [7,8]. Humanized and chimeric antibodies
can be constructed to circumvent the human anti-mouse antibody response elicited
by mouse antibody treatment of patients, which severely hampers the application of these
powerful molecules. The treatment of rheumatoid arthritis patients with doses of as high as
10 mg kg –1 cA2 chimeric antibody specific for TNFα [9], emphasizes that at present the production
and purification methods for these proteins have been optimized to such extent that
clinical studies can be considerably intensified.