Toxins, cancer treatment

These therapies are mainly used for cancer treatment and are considered as heat-toxin in TCM. When the cancer cells are killed, the body is severely injured too. The Yin and the Qi in particular are seriously depleted and weakened by the extreme heat. Moreover, these therapies can cause further disturbances in the body such as deficiency of Kidney-essence and blood, blood stagnation, bleeding,... 

The development of monoclonal antibodies (mAbs) has revolutionized cancer treatment, and several mAbs are today approved for clinical use. Treatment resistance is often a problem in mAbs-treatment where multiple treatment series are necessary [100]. Dmg response can be increased by binding mAbs to cytotoxic compounds, such as protein toxins, forming immunotoxins (ITs) [101]. The historical problems with first and second generation ITs are largely solved by the use of recombinant DNA technology where chimeric proteins consisting of the Fv-ffagment of an antibody and... 

Pastan, I. and FitzGerald, D. (1991). Recombinant toxins for cancer treatment. Science 254, 1173 1177. 

Finally, vaccination against cancer is beginning to emerge as a realistic possibility. It will be recalled that Coley s toxins were used to evoke an immune response in an early form of cancer treatment. Now the technique has been reinvented through the introduction of synthetic vaccines raised against portions of the glycoprotein coat of tumour cells. In phase II clinical trials carried out in Canada, the USA and the UK, more than 200 patients with colorectal cancer were treated with this type of vaccine. Most of them experienced the same periods of survival as patients treated with chemotherapy, but their quality of life was better, since they did not suffer from any adverse effects due to drugs. 

Thus, microorganisms have been used in cancer treatment. For example. Moss has a chapter about Coley s Toxins, a mixed bacterial vaccine, in the treatment of cancer (Moss, 1992, pp. 407 12). Moss calls the discovery of these toxins one of the most remarkable happenings in the history of cancer therapy. Discovered in the late nineteenth century by William B. Coley, M.D., chief surgeon at Memorial Hospital (now the Memorial Sloan-Kettering Cancer Center or MSKCC), who undertook a 40-year experiment in treating and even curing cancer. Coley s Toxins may be regarded as the basis for modem immunotherapy. 

Martin, W. 2006. Coley s Toxins A Cancer Treatment History. Townsend Letterfor Doctors and Patients, nos. 229/230 (February/March) 113-118. 

Ricin toxin is found in the beans of the castor plant, Ricinus communis. It is one of the most lethal and easily produced plant toxins. The toxin is present in the entire plant but is concentrated in its seeds. Ricin can be in the form of apowder, mist, or pellet, or dissolved in water or weak acid. It is a very stable substance and is not affected by extremes in temperature. Castor beans are processed throughout the world to make castor oil. Ricin is part of the waste mash produced when castor oil is made. Ricin irreversibly blocks protein synthesis. Ricin has some potential medical uses, such as bone marrow transplants and cancer treatment (to kill cancer cells). 

Morimoto, H., Yonehara, S., and Bonavida, B. (1993). Overcoming tumor necrosis factor and drug resistance of human tumor cell lines by combination treatment with anti-Fas antibody and drugs or toxins. Cancer Res. 53,2591-25%. 

Denileukin diftitox is a combination of the active sections of interleukin 2 and diphtheria toxin. It binds to high-affinity interleukin 2 receptors on the cancer cell (and other cells), and the toxin portion of the molecule inhibits protein synthesis to result in cell death. The pharmacokinetics of denileukin diftitox are best described by a two-compartment model, with an a half-life of 2 to 5 minutes and a terminal half-life of 70 to 80 minutes. Denileukin diftitox is used for the treatment of persistent or recurrent cutaneous T-cell lymphoma whose cells express the CD25 receptor. Side effects include vascular leak syndrome, fevers/chills, hypersensitivity reactions, hypotension, anorexia, diarrhea, and nausea and vomiting. 

Risk factors for the development of AML include exposure to environmental toxins, Hispanic ethnicity, and genetics.6 Of greater concern is the increased prevalence of AML as a secondary malignancy, resulting from chemotherapy and radiation treatment for other cancers. Alkylating agents, such as ifosfamide and cyclophosphamide, and topoisomerase inhibitors, such as etoposide, are linked to an increased risk of myelodysplastic syndrome (MDS) and AML.8... 

Intravesical infusion of linear PEI/pDNA polyplexes was evaluated in patients with superficial bladder cancer where intravesical therapy with bacillus Calmette-Guerin had failed [6, 224]. Patients had low grade superficial bladder cancer, which expressed H19. The therapeutic pDNA contains H19 gene regulatory sequences that drive the expression of an intracellular toxin. Escalating doses of 2-20 mg plasmid per intravesical treatment were applied, with responders continuing to receive polyplexes once a month every month for 1 year. The treatment resulted in complete ablation of the marker tumor, without any new tumors in four of the 18 patients (22% overall complete response rate). Eight of the 18 patients (44%) had complete marker tumor ablation or a 50% reduction of the marker lesion. 

Proleukin is a recombinant form of IL-2. It is approved for the treatment of malignant melanoma and renal cell cancer. Ontak (denileukin diftitox) is a fusion protein for the treatment of persistent or recurrent T-cell lymphoma. Activated T cells express lL-2 receptors. Ontak has a fragment that binds to the IL-2 receptor while the other part presents a diphtheria toxin to kill the activated T cell. 

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). 

IL-2 DAB389 (Ontak) Interleukin-2 (IL-2) Binds to IL-2 receptors expressed on cancer cells and T-cell lymphoma DAB389 is a binding-deficient variant of diphtheria toxin Cytotoxicity Approved for treatment of T-cell lymphoma... 

A link between bacteria and tumor therapy was found early, at the beginning of the XVIII century [10]. By the end of the XIX century, Coley [11] developed a treatment for cancer with a mixture of bacterial toxins. In 1943 Shear and Turner [4] found that the antitumor effect of Coley s toxin was due to endotoxins, and after several decades it was shown that the biological activity of LPS was due to the lipid A [5]. We investigated the structures of lipids A with regard to their antitumor activities [12], finding that the optimum in vivo activity is obtained with diglucosamines acylated by 3 long chain fatty acids. 

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