CRM197 a new immunotherapy for cancer | immunotherapy


	Sunday, 05 September, 2010

Science book

Cancer evolution is an example of competitive evolution. It is a warning that competition (darwinian evolution) is not the way to further evolution. Understand this for the sake of our planet and ourselves...

As a book on cancer evolution, the selfish cell deals with innovative concepts in evolutionary biology. Additionally, new ideas on cancer treatments are forwarded to researchers.

immunotherapy

CRM197 a new immunotherapy for cancer

dendritic_cells

Many years ago, diphtheria toxin (DT) showed antitumor activity in mice and in humans, but it was unclear whether this depended on the toxicity of the molecule only or on its strong inflammatory-immunological property as well. (Buzzi S., Cancer Res. 1982 May;42(5):2054-8). The same researchers, to deal with this open question, planned to treat a group of cancer patients with cross-reacting material 197 (CRM197).

Gc-maf cancer immunotherapy

...The once-weekly injection of minute amounts of Gc-MAF, just 100 nanograms (billionths of a gram), activates macrophages and allows the immune system to pursue cancer cells with vigor, sufficient to produce total long-term cures in humans..."

A report on the creation of a virus obtained genetically modifying a common adenovirus which could constitute a therapy against cancer has appeared recently in the scientific news. This virus would selectively infect cancer cells and force them to express a protein which calls for the intervention of macrophages, additionally stimulating them to multiply. This strategy would therefore help the body mounting a strong immune response against cancer cells.

Cancer immunity trick discovered

Cancer can spread only after having won the fight against the immune system. In the years scientists have discovered a number of strategies put in place by cancer cells to sneak out of the control of the immune system or even to counterfight it. Macrophages, a fundamental arm of immunity, should be put off for cancer affirmation.

They are key determinants in autoimmunity but have been indicated to play a crucial role in cancer immune-evasion (Franzke A, Hunger JK, Dittmar KE, Ganser A, Buer J Regulatory T-cells in the control of immunological diseases. Ann Hematol. 2006 Nov;85(11):747-58. Epub 2006 Jul 27). Increasing evidences support the existence of elevated numbers of these regulatory Treg cells in solid tumors and hematological malignancies.

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CRM197 a new immunotherapy for cancer

dendritic_cells

CRM197 is a nontoxic mutant of DT that shares the immunological properties of the native molecule and its ability to bind to heparin-binding epidermal growth factor (HB-EGF), the specific cell-membrane receptor for DT that is often overexpressed in cancer. 25 patients with various advanced tumors who were refractory to standard therapies (23 subjects) or had refused, in whole or in part, conventional therapies (2 subjects) were treated with CRM197 injected subcutaneously in the abdominal wall, on alternate days, for 6 days. Three different dosages (1.7, 2.6, or 3.5 mg/day) were used according to the patient's degree of immunological reactivity to DT/CRM197 (none, moderate, or high).After the first administration of CRM197, a significant increase in the number of circulating neutrophils and in the serum level of TNF-alpha was detected. Toxicities were minimal. Only patients with delayed-type hypersensitivity to DT/CRM197 had irritating skin reactions in the injection sites and a flu-like syndrome with fever. Pharmacokinetics showed a mean peak concentration (12.7 ng/ml) 12 h after the first injection and a mean half-life of 18.1 h. There were two complete and one partial responses (metastatic breast carcinoma, neuroblastoma, and metastatic breast carcinoma) lasting 4, 45+, and 15 months, respectively. Six cases of stable disease, lasting from 1 to 15 months, were also recorded. CRM197 injected subcutaneously elicited an inflammatory-immunological reaction, caused tolerable toxicities, was absorbed to a good extent into the circulatory system, and exerted some degree of biological antitumor activity. A possible role of neutrophils and TNF-alpha in the mode of action of the molecule has been hypothesized, but not yet confirmed. This interesting molecule is currently under investigation in a phase II clinical trial held in Japan by Prof. Mekada and collaborators. Results are expected impatiently in less than a year. The rational under the antitumor activity of this molecule is still to be fully elucidated. Anyway, it seems to hold the noteworthy property of reawaken the host immune system, often dormant or inefficient in cancer patients. An excerpt from Cancer Immunol Immunother. 2004 Nov;53(11):1041-8.

the DCA site

Tumor cells often preferentially use glycolysis to generate adenosine triphosphate (ATP), even in the presence of oxygen, a phenomenon known as aerobic glycolysis, or the "Warburg effect. DCA treatment appears to restore and to boost mitochondrial respiration in cancer cells, consequently causing cancer cell selective killing by a kind of "self-burning" effect.

Reform the FDA

Science constantly discovers new health treatments which are not made available to people because of money reasons. It is time to stand up against these fraud that prevents people getting treatments they need to survive. Read to understand and join action.

cell energy therapy

Leukemia cells metabolize fat to avoid cell death

Leukemia cells, like most cancers, are addicted to glucose to generate their energy, but new research shows that these cells also rely on fatty acid metabolism to grow and to evade cell death.

dca and sugar

DCA promoters recommend taking caffeine and extra thiamine (vitamin B1), hoping that this will help the DCA work better and reduce potential risks of nerve damage. In a survey conducted by the DCA site (www.thedcasite.com) a certain number of heavy tea or coffee drinkers observed astounding responses, even remissions. Here we propose that it could be the sugar contained in those drinks to have helped the DCA mote than, or maybe instead of, caffeine or theophylline.

The DCA therapy

apoptosis

In the review paper "Dichloroacetate (DCA) as a potent..." appeared in the Online first session, in September issue of BJP, Prof. Michelakis most interestingly underlines the importance of targeting the peculiar "aerobic glycolytic" metabolic status of tumors. He suggests that the "Warburg effect", as the phenomenon is more commonly known in the literature, can be modulated by unlocking a mitochondrial impairment in cancer cells and that this could be a very promising strategy to fight cancer.

Can metformin boost DCA?

By itself, metformin was ineffective in treating tumors. In a one-two punch, metformin reduced tumors faster and prolonged remission in mice longer than chemotherapy alone, apparently by targeting cancer stem cells, report Harvard Medical School researchers in the Sept. 14 advance online Cancer Research.

cancer energetic signature

In the last issue of Translational Oncology (2009, 2, pp. 138-145) a report appeared confirming that cellular bioenergetics is a central issue of investigation in cancer biology.

ukrain or oxamate after dca

DCA is in clinical trials and results are expected with great interest. Meanwhile stories can be heard from people, even read on the internet, that tell us that they or their relatives have benefited from using DCA against cancer expecially when combining it with other treatments.

green tea synergize with dca

Recently patients, writing on the DCA site, have reported that adding green tea extracts to their DCA experimental anticancer regimen gave them benefits in term of cure efficacy.