R

Figure 19.32 Diagram of effects of intramuscular injection of DNA plasmid vaccine. In this scenario, the vaccine also contains a gene for a cytokine, granulo-cyte-macrophage colony-stimulating factor (GM-CSF). Since muscle cells express little, if any, MHC molecules, dendritic cells acquire the antigen by secretion from or apoptosis of muscle cells, with subsequent presentation to appropriate cytotoxic T cells (CTL). In order to enhance or "cross-prime" the reaction, the GM-CSF produced by the muscle cell containing this gene after transfection recruits and stimulates dendritic cells to the site with enhancement of production of CTLs. ( Adapted from Giese, 1998, with permission of the author and publisher.)

target cells

Figure 19.32 Diagram of effects of intramuscular injection of DNA plasmid vaccine. In this scenario, the vaccine also contains a gene for a cytokine, granulo-cyte-macrophage colony-stimulating factor (GM-CSF). Since muscle cells express little, if any, MHC molecules, dendritic cells acquire the antigen by secretion from or apoptosis of muscle cells, with subsequent presentation to appropriate cytotoxic T cells (CTL). In order to enhance or "cross-prime" the reaction, the GM-CSF produced by the muscle cell containing this gene after transfection recruits and stimulates dendritic cells to the site with enhancement of production of CTLs. ( Adapted from Giese, 1998, with permission of the author and publisher.)

the bladder (Melekos, 1995). In general, however, nonspecific immunostimulation of the immune system has not found a major place in the immunotherapy of human neoplasia.

Antibody Therapy of Neoplasia

Although polyclonal antibodies had been raised against a variety of antigens from many neoplasms, their usefulness in therapy was never completely realized, primarily because the antibody source, usually an animal, disappeared with the death of the animal or the formation of multiple cross-reactive antibodies on repeated immunizations. In addition, the host response to the foreign antigen (antibody) usually prevented its use after a limited time period. It was not until the development of monoclonal antibodies that could be continuously produced in mice and/or tissue culture or even in human cells that the antibody therapy of neoplasia became more realistic. A diagram of the technique of producing monoclonal antibodies in mice is seen in Figure 19.33. Monoclonal antibodies specific for antigens on neoplastic cells can induce a variety of responses, including apoptosis, interference with ligand-receptor interactions, modulation of chemotherapeutic cytotoxic effects, and both complement-mediated and antibody-directed cyto-toxicity (Weiner, 1999). While a number of clinical trials with various antibodies have been and are under study (cf. Scott and Welt, 1997), one of the most successful and presently clinically useful monoclonal antibodies is that directed toward the HER-2/neu cellular oncogene present on the surface of a variety of neoplastic cells. This molecule is a member of the epidermal growth factor receptor family and presumably functions as a growth factor receptor (cf. Disis and Cheever, 1997). Most normal tissues express this protein only slightly if at all, whereas up to 34% of breast cancers overexpress the molecule, many times probably owing to amplification (cf. Ross and Fletcher, 1999; Menard et al., 2000). Although the use of this monoclonal antibody therapy is usually carried out according to standard therapy, up to 37% of patients treated with the antibody developed objective response and disease stabilization (cf. Ross and Fletcher, 1999).

Immune Conjugates in Antibody Therapy

Monoclonal antibodies to specific antigens on neoplastic cells may also be used as carriers for specific molecules that are toxic to the cell. In theory, this would then selectively eliminate the neoplastic cell carrying the antigen recognized by the monoclonal antibody. A diagram of such a system is seen in Figure 19.34. A variety of different toxins conjugated to monoclonal antibodies reactive with specific surface antigens have been studied (Kreitman, 1999).

In addition to the use of various toxins conjugated to monoclonal antibodies, radioactive elements and compounds have also been utilized. In a very similar manner, as noted in Figure 19.34, an antibody containing a conjugate of a radioactive element or compound is utilized in the same way. In this way the radioactivity enters the cell, thereby destroying it and the surrounding cells. In theory, the selectivity of this type of therapy should be quite high, and several different radioactive monoclonal antibody conjugates are now in clinical use (cf. DeNardo et al., 1998; White et al., 1999).

Adoptive Cellular Immunotherapy

As noted earlier in this chapter, several cellular populations, notably NK cells and macrophages as well as some dendritic cell populations, can exhibit effective immune responses against neoplasms. However, it was not until methods were developed to produce large populations of such cells that could be reinfused into the autologous donor that the use of cells in the immunotherapy

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book


Post a comment