Cell-Kill Principle

Colony-stimulating factors were investigated a decade ago as "priming agents" to recruit cells into the cycle, so theoretically there was a greater leukemia cell kill. Most studies were negative and showed no incremental increases in CR rates. Recent data suggesting that there is improved disease-free survival has renewed interest in this principle. 

Fig. 7.1. Principles of tumor cell kill by antibodies bispecific antibody-mediating effector-tumor cell interaction, naked antibody mediating antibody dependent cellular cytotoxicity...

Homogeneous dose distribution. Tumor cell kill depends on intrinsic radiosensitivity, local physiology and biochemical status of the tumor subvolumes. In principle, the whole tumor can be covered by the radiation dose required to kill all tumor cells. 

Inspection of the death curves obtained from viable count data had early ehcited the idea that because there was usually an approximate, and under some circumstances a quite excellent, linear relationship between the logarithm of the number of survivors and time, then the disinfection process was comparable to a unimolecular reaction. This imphed that the rate of killing was a function of the amount of one of the participants in the reaction only, i.e. in the case of the disinfection process the number of viable cells. From this observation there followed the notion that the principles of first-order... 

A number of anticancer drugs that kill cells by destroying their DNA via free radicals are used in the clinic. They show a most remarkable chemistry. Some of it is fairly well understood. Where important open questions remain, attention is drawn to these in order to elicit future studies that are urgently needed for a better understanding of the underlying mechanistic principles. 

The primary clinical targets of immunotoxins are tumors, based on the principle that the MAb will target the toxin to the tumor cells and the highly toxic moiety will then kill the cancer cells. Examples of toxins are ricin, diphtheria toxin and abrin, which are all glycoproteins. Their toxicity is based on their ability to block protein synthesis at the ribosomal protein assembly site. They are normally extremely toxic and not suitable for therapeutic purposes because they induce liver and vascular toxicity, even at low dose levels. 

Fig. 3.3 shows the principle behind the design of immunotoxins. A number of protein toxins of bacterial and plant origin are useful for the production of immunotoxins. These include the diphtheria toxin and pseudomonas exotoxin from bacteria, and ricin, arbin, pokeweed antiviral proteins, saporin, and gelonin from plants (Pastan et al, 1986 Pastan and FitzGerald, 1991). All of these toxins kill cells by entering the cells, and enzymatically inactivating the translational machinery of the cells. Some, such as diphtheria toxin, arbin, and ricin, are composed of two protein chains, A and B. The B chains bind to the cell-surface... 

For thousands of years, perishable foods such as fish, olives, and vegetables have been preserved in salt or brine. The high salt concentration is hypertonic to bacteria cells, and kills them by dehydration before they can cause the food to spoil. Preserving fruit in sugar (jams, jellies) works on the same principle. 

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