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| William Coley |
Se plantea que la constatación de las relaciones entre la infección y la regresión del cáncer se remontan al menos al siglo XVIII, antecediendo las ideas y pruebas de Coley hasta desarrollar sus toxinas.
Concretamente se había observado cierta relación entre la infección por erysipelas y la remisión de ciertos tumorres y se dice que Anton Chekhov recogió datos sobre esa relación en 1884.
Coley comenzó sus investigaciones después de la muerte de uno de sus primeros pacientes a causa de un sarcoma. El nombre de esta paciente era Elizabeth Dashiell.
Se dice que la frustración que le produjo este revés condujo a Coley a emprender su investigación y a plantear la evidencia de una aparente relación entre la infección por microroganismos y la regresión del cancer, lo cual publicó por primera vez 1891.
Hacia 1893 Coley comenzó a combinar Streptococcus pyogenes y Serratia marcescens, apoyandose en las investigaciones de G.H. Roger que indicaban que esta combinación parecía tener una mayor virulencia. Las llamadas Toxinas de Coley comenzaron a ser utilizadas contra distintos tipos de cáncer ese mismo año y su uso se extendió hasta 1963. Durante la década del 20 del pasado siglo solo Parke-Davis producía y distribuía las toxinas en estados unidos hasta que en 1962 en medio de las controversias sobre la Thalidomida y la Enmineda Kefauver Harris Amendment se hizo ilegal la prescripción de las toxinas fuera de ensayos clínicos. desde entonces se han realizado varios ensayos clínicos con resultados no contundentes
Las Toxinas deColey también fueron producidas por la compañía farmacéutica alemana Südmedica y vendidas bajo el nombre comercial de Vaccineurin. Sin embargo la producción fue detenida en 1990 debido a la falta de re-aprobación del Instituto Federal Alemán para los Medicamentos y Dispositivos Médicos.
Hipótesis sobre la efectividad de las Toxinas de Coley
Existen varias hipótesis sobre el funcionamiento y efectividad de las Toxinas de Coley
Los macrófagos
Una idea sostenida es que los macrófagos están en dos modos fundamentales, uno denominado "modo de reparación" que puede fomentar el desarrollo del cáncer o en "modo defensa" que ayuda a combatirlo. Pero para que el modo defensa sea puesto en marcha debe haber un agente reconocido como enemigo y como las células malignas no son detectadas como enemigas es necesario despertar el modo defensa de los macrofagos estimulando una infección, la cual produce fiebre.
La fiebre como parte de la respuesta inmunologica no sólo produce aumento de la temperatura sino que además desencadena procesos relevantes para la destrucción de las células malignas.
Es por ello que la fiebre se considera un requisito para que las Toxinas de Coley sean efectivas.
Factor de necrosis tumoral e interleukinas
Tumor Necrosis Factor and Interleukin[edit]
One of the agents in Coley's Toxin that is thought to be biologically active is a lipopolysaccharide which causes fever.[21] The resulting fever from the lipopolysaccaride is thought to increase lymphocyte activity and boosts tumor necrosis factor (TNF). Tsung and Norton in Surgical Oncology reported that the active agent was thought to be interleukin-12, rather than TNF.[22]
Streptokinase[edit]
Another hypothesis argues that streptokinase (produced by bacteria of type "streptococcus" together with plasminogen from the patient) is the active agent of Coley's toxins.[23][24] This hypothesis is supported by the fact that streptokinase has been associated with successful treatment of thromboangiitis obliterans.[25]
Anti-angiogenesis[edit]
In addition to the mechanisms above, Coley's toxins might be antiangiogenic – suppressing the formation of new blood vessels which are vital to the growth of tumors.,[26] however, angiogenesis is not a biochemical cause by itself but needs external triggers.
Dendritic cells[edit]
A robust fever, which occurs in response to Coley fluid, generates inflammatory factors with co-stimulatory activity, which activate resting dendritic cells (DC), leading to the activation of anergic T cells, maybe accomplished by a second process, where a possible physical damage of cancer cells leads to a sudden supply of cancer antigens to DC.,[5][19]
PAMP[edit]
Recently (2008), an immunological explanation binding together immunological data with findings about spontaneous regression and epidemiological data indicating a lowered risk to develop cancer later after common infections, has been published.[27] According to this hypothesis, pathogenic substances produced by bacteria, viruses, infectious fungi and other pathogens, but not human tissue, called 'pathogen associated molecular pattern' (PAMP) lead to activation and maturation of tumor-antigen loaded dendritic cells. One PAMP thought to play a major role is the unmethlyated CpG motif found in bacterial DNA. The CpG motif is recognized by toll like receptor 9 (TLR9) and can induce a strong TH1 response.
Overview
Modern forms of immunotherapy are based on a better understanding of the effects of the immune system on cancer and are likely to be more effective. Although some practitioners continue to recommend and give Coley toxins, this treatment fell out of use decades ago by most oncologists in favor of more modern treatments. To most mainstream oncologists, the value of Coley's research was as a foundation for much of modern cancer immunotherapy. Some clinical research has been done on this very early form of cancer immunotherapy, but the strength of evidence is limited by the small number of cases and the fact that most research was done in the early part of the 20th century, when research methods were less rigorous than they are now. Some studies found that Coley toxins improved survival for people with certain forms of cancer, while other studies did not find a significant benefit.
How is it promoted for use?
Supporters claim Coley toxins stimulate the immune system in people with cancer, which helps to fight off disease. Some supporters also believe that tumor cells are more sensitive to heat than normal cells and that the high fever caused by Coley toxins helps to rid the body of cancer.
What does it involve?
Coley toxins are injected directly into the tumor or into the bloodstream in increasing daily doses until a fairly constant state of fever is reached. Treatment is often continued for several months. Patients are monitored closely for side effects and to control fevers as they develop.
The original formula for Coley toxins is no longer used in the United States, although similar formulas are used in at least one clinic. Coley toxins are used in Central America, Germany, and China, but it is not clear whether they are using the original Coley toxins or a combination of Coley toxins and other bacteria.
What is the history behind it?
Coley toxins were first used in the 1890s by William B. Coley, MD, a bone surgeon at Memorial Hospital in New York City (now Memorial Sloan-Kettering Cancer Center). After his attempt to save a young woman from bone cancer failed, Dr. Coley began reviewing bone cancer cases. He noted that cancer patients in whom bacterial infections developed after surgery seemed to have better outcomes than those who did not. He believed the bacterial infection helped to stimulate the immune system, causing it to fight off cancer cells. At first, Coley injected live bacteria into cancer patients, but because of the danger of serious or even fatal infection with that approach, he began using bacteria that had been killed. His treatment was controversial, despite some reports of cancer regression with its use. Dr. Coley passed away in 1936.
Different formulas of Coley toxins were made by several drug companies in the United States in the first half of the twentieth century. They were used to treat patients with a variety of types of cancer up until the early 1950s, when other forms of cancer treatment became more widely used.
Dr. Coley's daughter, Helen Coley Nauts, published several papers documenting her father's results. She also founded the Cancer Research Institute in New York in 1953, which continues to study how immunology can help diagnose and treat cancer.
Combinations of Coley toxins and other strains of bacteria are still being used at the Waisbren Clinic in Milwaukee, although the clinic recommends that patients try conventional treatments first. Coley toxins or similar treatments are also used in clinics in several other countries. There does not appear to be any active clinical research at this time into the use of the original Coley toxin formula. At least one pharmaceutical company is studying the use of pieces of DNA that may have contributed to the effectiveness of Coley toxins.
Dr. Coley is credited with pioneering the field of cancer immunotherapy. Immunotherapy is sometimes used alone but is more commonly combined with standard cancer treatments or used after conventional treatment. At this time, immunotherapy has a relatively small role in treating people with the most common types of cancer. However, researchers are optimistic that more effective immunotherapies can be developed that will have a greater impact on the outlook for people with cancer.
What is the evidence?
Scientific evidence suggests Coley toxins or other mixed bacterial vaccines may have a role in treating cancer when combined with other treatments. Coley reported his results as case series, which was the way most research was done in the early twentieth century. This format limits the ability of modern researchers to evaluate his findings. A retrospective review by researchers at the former University of Texas Center for Alternative Medicine compared 128 patients treated with surgery and Coley toxins between 1890 and 1960 to 1,675 similar patients treated in 1983 with conventional methods. The review found that survival rates for Coley's patients were about the same as those treated with more modern conventional methods. The University of Texas researchers point out that the study was limited by small sample size, short duration, and selection bias. More research would be needed to determine what benefit, if any, this therapy might have for people with cancer.
Results of three randomized clinical trials of Coley toxins or mixed bacterial vaccines have been published or presented. A 1962 article reported that more than one of 4 patients treated with Coley toxin showed objective improvement, whereas none of the patients who received a control vaccine made from different bacteria did.
A randomized trial of patients with nodular lymphoma (now known as follicular lymphoma) was discussed at a 1983 conference. Of the patients who received Coley toxins and chemotherapy, 85% had a complete response, in which all signs of cancer disappeared. This was compared with a 44% complete response rate in the patients who did not receive Coley toxins. Nodular lymphoma is among the cancer types that respond well to modern immunotherapy with monoclonal antibodies, however, so the relevance of this study to modern oncology practice is uncertain. The study was never reported in full in a journal, which has led some researchers to wonder whether long-term follow-up confirmed this degree of benefit.
Results of a Chinese study of patients with advanced liver cancer (hepatocellular carcinoma) were published in 1991. The study reported a significant benefit for patients with liver cancer that was too advanced for surgery, but no significant benefit in those who had surgery. Dr. Coley's earlier reports noted greatest success with sarcomas and lymphomas, and he eventually stopped treating patients with carcinomas. Reasons for the discrepancy between the older results and this more recent study are not clear.
Although Coley toxins are often regarded as an historic key step to modern immunotherapy, much has been learned about the immune system since that time. Modern immunotherapy is likely to be of greater value, especially in treating certain cancers, such as lymphoma, renal cell (kidney) cancer, and melanoma.
Several recent laboratory and animal studies have been done to find out how Coley toxins might have worked, why they seemed useful for some cancer types and not others, and how modern methods could be used to develop immunotherapies that are more consistently effective and less toxic. Some immunologists believe that Coley toxins stimulated production of IL-12, a substance that can activate the immune system to attack cancer cells. Laboratory and clinical studies of IL-12 are currently in progress.
Complicaciones y efectos secundarios
No se han encontrado evidencias de interacciones con otros medicamenhtos, alimentos o suplementos dietéticos
Las bacterias debilitadas presentes en la fórmula de Coley pueden producir nauseas y vomitos y algunos síntomas menos frecuentes pueden ser dolor de cabeza, dolor de espalda, escalofríos, dolor en el pecho y reacciones de tipo shock y las mujeres embarazadas o amamantando no deben consumir este producto.
Para la elaboración de este artículo se han usado extensamente la entrada de la Wikipedia dedicada a el y la revisión que se hace de este tratameinto en la página de la American Cancer Society
Empresa canadiense que la produce
http://mbvax.com/index.php/historical-results/
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