Tumour cell targeting

A specific peptide motif linked to the chemotherapeutic molecule can enhance its efficacy, reduce their toxicity and also improve tumour cell targeting.45,51,52 Therefore, a range of glycoporphyrins 59 and 60 bearing the Arginine-Glycine-Aspartate (RGD motif) moiety were synthesised (Fig. 6). 

Radiotherapy is a local treatment aiming to achieve local control or cure of locally confined tumours. It cannot treat metastases. Radiotherapy may be administered as external beam radiotherapy with X-rays or gamma rays, in sealed radioactive sources (e.g. prostate brachytherapy), or unsealed sources (e.g. orally administered radioiodine for thyroid cancer, intravenous strontium-89 for bone metastases). In external beam radiotherapy, the X-ray or gamma ray beams are targeted at the tumour to damage and kill the tumour cells. Inevitably, surrounding normal tissues are also affected resulting in the early and late side effects of radiotherapy. 

The treatment of tumours in the liver with drug targeting preparations is hampered by the lack of tumour specifity of most preparations. Liposomes incorporating the immunomodula-tor muramyl tripeptide phosphatidylethanolamine have been used as an aspecific approach to increasing the number of tumouricidal macrophages in the liver in order to prevent the development of metastases [99].To date, the greatest tumour cell specificity has been obtained... 

Strategies for Specific Drug Targeting to Tumour Cells... 

The success of treating tumours, especially solid tumours, by systemic therapy depends on various characteristics of the tumour. Besides the importance of intrinsic drug activity and the potential targets within the tumour cells, drug pharmacokinetics and whole body distribution, site of delivery and the ability of site-specific targeting (affinity) are important features. 

In the following sections tumour cell-directed targeting and intracellular delivery of drugs will be discussed. This includes crucial factors such as tumour structure and physiology as well as physiological, cellular, molecular, biochemical and pharmacokinetic barriers. 

Strategies to Deliver Drugs to Targets within the Tumour (Cells)... 

As the specificity and availability of the target epitope expressed by the tumour cells are important determinants for therapeutic outcome, the most interesting antigenic targets will be discussed below. 

Another approach to selectively inducing tumour cell kilhng is by the use of bispecific monoclonal antibodies (BsMAb).They combine the specificity of two separate antibodies within one molecule and cross-hnk an effector killer cell or a toxic molecule with the target cell to be destroyed [75]. There are three major approaches for creating BsMAbs.They can be obtained by chemical cross-linking of two MAbs, by fusing two hybridomas [76], or by genetic... 

Cytotoxic drugs including toxins such as saporin, ricin A chain, vinca alkaloids, and radioisotopes have been delivered to tumour cells with BsMAbs that bind to the drug/toxin with one arm and to a surface molecule on the targeted cell with the other arm. This approach has proven successful in animals as e.g. shown by Schmidt et al. [78]. 

Cytotoxic effector cells have also been cross-linked to tumour cells via BsMAb (Figure 8.3). The BsMAb activates the cytotoxic activity of the effector cell on bridging it to the target cell. Several effector cells, including phagocytic cells, natural killer (NK) cells and T lymphocytes, can mediate cellular cytotoxity [37,75,79,80]. Adequate pre-activation of the effector cells is an important requirement in these methods of drug delivery. In the case of T... 

---