Drug Targeting Strategies in the Clinic

Of the target epitopes suggested for use in tumour vasculature directed drug targeting strategies (Table 9.1), those discussed above seem to be the most promising for development for clinical application. A few have not been extensively studied for this purpose but may also be interesting candidates, and are therefore discussed below. 

What has been achieved until now In the year 2001, several liposome and antibody based strategies have been or will soon be approved for clinical application, some for the treatment of cancer, some for the treatment of bacterial infections, some for chronic inflammatory diseases. Furthermore many monoclonal antibodies without a drug or pharmacologically active molecule attached are in the clinic. Their intrinsic targeting and effector function is obviously sufficient for the pharmacological effect. 

Only a few polymer or protein based drug targeting strategies have reached the clinic and an important question in the coming years will be whether these strategies eventually will reach it. All will depend on their effectiveness and improved toxicity profiles as compared to free drug only and the ease of their production at large scale. 

These hypotheses have been supported by a series of preclinical studies that employed MTX and anti-MTX Fab as model drugs [2,4,5]. However, MTX is not an ideal drug for future clinical applications of the inverse targeting strategy, due to its limited ability to penetrate solid tumors [13] and due to its relatively low potency. TPT may be an ideal drug for use in the proposed approach this agent is a preferred therapy for metastatic, refractory ovarian cancer, and TPT is very potent, with a maximum tolerated dose of -5 mg in humans (via i.p. instillation) [14]. 

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