Direct tumor cell kill

ANNE C.E. MOOR, BERNHARD ORTEL AND TAYYABA HASAN 

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The rationale for concurrent chemoradiation is that the ChT can augment local-regional control by both direct tumor cell killing and radiosensitization at the same time as it addresses systemic micrometastases. Unfortunately, this also has the potential to increase radiation-related mucosal acute toxicity, predominantly esophagitis and pneumonitis. Thus, some of the early trials of concurrent therapy used either attenuated dose ChT or split course RT to ameliorate potential cotoxicity. These trials showed that concurrent therapy is feasible and, as with the sequential approach, improves outcome. 

B.W. Henderson, V.H. Fingar (1989). Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. Photochem. PhotobioL, 49, 299-304. 

Ideally, one would like to measure the mass transfer rates and concentrations in each compartment of a tissue as a function of both time and space and develop precise mathematical models on the basis of these data. Such models could then be used to predict spatial and temporal concentrations of various agents in a variety of normal and neoplastic tissues. Since the selective tumor cell kill depends on the concentration-time history of a drug, such information could be used in developing optimal dose schedule of anticancer agents. However, there are several practical problems in carrying out such detailed measurements directly, and in developing such detailed, dynamic, predictive mathematical models. Nevertheless, it is possible to obtain considerable useful information about mass transfer in tumors, using the experimental and theoretical approaches discussed in the next two sections. 

There are various gene therapy approaches that are being developed for the treatment of cancer. They are aimed at inhibiting molecular pathways underlying malignant cell transformation. In other cases, tumor cell ablation by directly applying cell-killing... 

Tumor cell killing by granulocytes was most potently triggered by FcaRI-directed bispecific constructs [92]. Recent studies indicate that simultaneous engagement of FcaRI and FcyRI results in enhanced PMN-mediated tumor cell lysis [114], suggesting that new Ab cocktails, e.g. combinations of IgG and IgA Abs, may improve the efficacy of current clinical protocols. 

Colloidal gold-labeled (strept)avidin can be used as highly sensitive detection reagents for microscopy techniques (Cubie and Norval, 1989) (Chapter 24). Finally, cytotoxic substances coupled to (strept)avidin can be used to direct cell-killing activity toward a tumor-cell-bound, biotinylated monoclonal antibody (or other targeting molecule) for cancer therapy (Hashimoto et al, 1984) (Chapter 21). 

About a 100 years ago, Coley observed tumor regression after application of a mixture of bacterial toxins. This experiment made the foundation of immune therapy for cancer, which only recently became a promising treatment and an efficient alternative to chemotherapy. In contrast to chemotherapy (1), this new treatment does not kill tumor cells directly rather it enhances the sensitivity of the patient s own immune system against tumor cells with all the potential positive aspects like high selectivity of treatment and much less side effects (2). 

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