Science Current Events | Science News | Brightsurf.com
 

Natural mechanism for immune suppression paves way for cancer trials

March 29, 2007
A natural mechanism pirated by tumors and HIV to evade the immune response is opening the door to better treatment for these conditions, researchers say.

The National Cancer Institute and Iowa biopharmaceutical company NewLink Genetics are pursuing FDA approval to move forward with cancer trials of a drug that inhibits the mechanism, an enzyme called indoleomine 2,3-dioxegenase, or IDO, says Dr. Andrew Mellor, director of the Immunotherapy Center at the Medical College of Georgia.

He will deliver seminars about the biology and immunology of the mechanism at the Keystone Symposium on "The Potent New Anti-Tumor Immunotherapies," in Alberta, Canada, March 28-April 2 and the World Immune Regulation Meeting April 10-16 in Switzerland.

Immune cells, particularly those in the mucosal surfaces of the gut, lungs and eyes, express IDO to mediate inflammation triggered by the constant assault of substances from outside the body.

Now, scientists know cancer in humans and mice also attract cells that express IDO, which degrades tryptophan, an amino acid essential to survival of immune system orchestrators called T-cells. MCG researchers are still exploring how IDO interacts with other cells to amplify immune suppression.

A team of MCG scientists, led by Dr. Mellor and his colleague, MCG pediatric oncologist Dr. David Munn, showed in 1998 that the fetus also expresses IDO to help avoid rejection by the mother's immune system. When they used an orphan drug known to suppress IDO in pregnant laboratory mice, fetuses were rejected.

The findings, published in Science, led the scientists to suspect and later prove that tumors and some viruses, including HIV, express it as well.

"Cancers should evoke a response from the immune system and don't," says Dr. Mellor. "That is a big question in the immunology field: Why don't they?"

IDO appears to be one reason. "What (cancers) do, we think, is make a protective cocoon so the immune system does not attack the tumor, so that gives you the therapeutic opportunity. If you stop IDO from blocking the response, you should allow the response, so now the specificity of the immune system is brought to bear directly on tumor cells."

Clinical trials, likely to begin this year, will determine whether a slightly modified version of the orphan drug researchers use in the lab, does just that.

NCI has produced kilogram quantities of the IDO inhibitor compound and contracted with a series of labs to do the studies required before studies can move from the laboratory to humans.

"The IDO inhibitor should result - and that is why we need to do the trials because we don't know for sure until we do - in better immunity directed against cancer cells," Dr. Mellor says.

Investigators already have shown that the IDO inhibitor works synergistically with chemotherapy in animal models of cancer. While chemotherapy knocks out some of the immune system's suppressive pathways, the IDO inhibitor prevents cancer cells from tricking the system into ignoring them again.

"Chemotherapy is toxic to cancer cells, but the problem is the cells come back so you don't completely eradicate the tumor. One of the main reasons they come back is the tumor already has established an environment which helps protect it, even after chemotherapy," Dr. Mellor says.

Although the IDO inhibitor will first be studied alone, he believes it will become part of the treatment cocktails that are becoming the standard for cancer care, possibly enabling less toxic doses of other drugs to be used.

Another goal for IDO suppression is to treat chronic infections that induce this mechanism, Dr. Mellor says.

"This mechanism is induced by pathogens to protect themselves from host immunity," says Dr. Mellor. "HIV certainly is a potent inducer of this mechanism." He suspects other diligent viruses and bacteria are as well.

"This is obviously an evolutionary adaptation that the pathogen has to protect it from being eliminated by the host," he says. "That is why the infection does not go away. In the case of HIV, we know it persists for decades, and in those decades it's slowly eating away at the immune system so that it becomes unable to deal with the infection. That is where AIDS comes from. The current standard of care for HIV patients is to slow that process, that wearing-down process of the immune system."

In 2002, MCG researchers showed that dendritic cells, which present antigens to T cells, express IDO. "If they express IDO, it's an important control point," Dr. Mellor says of research published in the Sept. 13, 2002 issue of Science.

"IDO has been known for decades," he says. "What was not known was IDO activity was regulating the adaptive immune response."

Medical College of Georgia


Related Immune Suppression Current Events and Immune Suppression News Articles


Rapid test to diagnose severe sepsis
A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

Survival Molecule Helps Cancer Cells Hide From the Immune System
A molecule that helps cancer cells evade programmed self-destruction, an internal source of death, might also help malignant cells hide from the immune system, an external source of death.

Drug regimen enough to control immune disease after some bone marrow transplants
Johns Hopkins and other cancer researchers report that a very short course of a chemotherapy drug, called cyclophosphamide, not only can prevent a life-threatening immune response in some bone marrow transplant recipients, but also can eliminate such patients' need for the usual six months of immune suppression medicines commonly prescribed to prevent severe forms of this immune response.

Immune function predicts infection risk among child trauma patients
Researchers studying critically ill children with traumatic injuries have identified an immune marker that predicts which patients are likely to develop a hospital-acquired infection.

Mechanism, and possible treatment, for immune suppression in liver disease uncovered
The mechanism which underlies the susceptibility of liver disease patients to life-threatening infection has been uncovered by Wellcome Trust-funded medical scientists, who have also suggested a possible treatment to reverse immune suppression in these patients.

La Jolla Institute discovers new mechanism for unleashing immune system against cancer
A major discovery that brings a new drug target to the increasingly exciting landscape of cancer immunotherapy was published yesterday by researchers from La Jolla Institute for Allergy and Immunology and their collaborators from other institutes.

Brisbane's drinking water linked to infections
Brisbane's water supply has been found to contain disease carrying bugs which can be directly linked to infections in some patients, according to a new study by QUT.

New clues found to preventing lung transplant rejection
Organ transplant patients routinely receive drugs that stop their immune systems from attacking newly implanted hearts, livers, kidneys or lungs, which the body sees as foreign.

Programmed cell death activates latent herpesviruses
Researchers have found that apoptosis, a natural process of programmed cell death, can reactivate latent herpesviruses in the dying cell.

Ohio State researchers restore immune function in spinal injured mice
In a new study, researchers at The Center for Brain and Spinal Cord Repair at The Ohio State University Wexner Medical Center show that is possible to restore immune function in spinal injured mice.
More Immune Suppression Current Events and Immune Suppression News Articles

Cancer Immunotherapy, Second Edition: Immune Suppression and Tumor Growth

Cancer Immunotherapy, Second Edition: Immune Suppression and Tumor Growth
by George C. Prendergast (Editor), Elizabeth M. Jaffee (Editor)


There has been major growth in understanding immune suppression mechanisms and its relationship to cancer progression and therapy. This book highlights emerging new principles of immune suppression that drive cancer, and it offers radically new ideas about how therapy can be improved by attacking these principles. Following work that firmly establishes immune escape as an essential trait of cancer, recent studies have now defined specific mechanisms of tumor immune suppression. It also demonstrates how attacking tumors with molecular targeted therapeutics or traditional chemotherapeutic drugs can produce potent anti-tumor effects in preclinical models. This book provides basic, translational, and clinical cancer researchers with an indispensable overview of immune escape as a critical...

Tumor-Induced Immune Suppression: Mechanisms and Therapeutic Reversal

Tumor-Induced Immune Suppression: Mechanisms and Therapeutic Reversal
by Dmitry I. Gabrilovich (Editor), Arthur A. Hurwitz (Editor)


Tumor-Induced Immune Suppression - Prospects and Progress in Mechanisms and Therapeutic Reversal presents a comprehensive overview of large number of different mechanisms of immune dysfunction in cancer and therapeutic approaches to their correction. This includes the number of novel mechanisms that has never before been discussed in previous monographs.The last decades were characterized by substantial progress in the understanding of the role of the immune system in tumor progression. Researchers have learned how to manipulate the immune system to generate tumor specific immune response, which raises high expectations for immunotherapy to provide breakthroughs in cancer treatment. It is increasingly clear that tumor-induced abnormalities in the immune system not only hampers natural...

Cancer Immunotherapy: Immune Suppression and Tumor Growth

Cancer Immunotherapy: Immune Suppression and Tumor Growth
by George C. Prendergast (Editor), Elizabeth M. Jaffee (Editor)


There has been major growth in understanding immune suppression mechanisms and its relationship to cancer progression and therapy. This book highlights emerging new principles of immune suppression that drive cancer and it offers radically new ideas about how therapy can be improved by attacking these principles. Following work that firmly establishes immune escape as an essential trait of cancer, recent studies have now defined specific mechanisms of tumoral immune suppression. It also demonstrates how attacking tumors with molecular targeted therapeutics or traditional chemotherapeutic drugs can produce potent anti-tumor effects in preclinical models. This book provides basic, translational, and clinical cancer researchers an indispensable overview of immune escape as a critical trait...

The Immune System Cure: Optimize Your Immune System in 30 Days-The Natural Way!

The Immune System Cure: Optimize Your Immune System in 30 Days-The Natural Way!
by Lorna Vanderheaghe (Author)


What causes one person to catch a cold or flu and another to avoid it? Why do serious outbreaks of infectious diseases leave some individuals untouched? What allows someone to be incapacitated by allergies? The answer lies within nature itself-our immune system. The Immune System Cure provides simple techniques for supercharging your immune system to resist and prevent disease. Through diet, exercise, stress reduction and nutritional supplements, including plant sterols and sterolins, you can harness the power of your immune system in just 30 days and help it combat: Antibiotic-resistant bacteria Fibromyalgia Allergies Hepatitis C Tuberculosis Cancer Rheumatoid arthritis and other autoimmune diseases Chronic fatigue syndrome and more Now you can maintain a healthy natural resistance to...

Tumor-Induced Immune Suppression: Mechanisms and Therapeutic Reversal

Tumor-Induced Immune Suppression: Mechanisms and Therapeutic Reversal
by Dmitry I. Gabrilovich (Editor), Arthur A. Hurwitz (Editor)


This monograph, for the first time, presents a comprehensive overview of different mechanisms of immune dysfunction in cancer as well as therapeutic approaches to their correction. It discusses a number of new mechanisms that have never been discussed in a monograph before: T-cell inhibitory molecules, regulatory tolerogenic DCs, and signaling pathways in antigen-presenting cells involved in T-cell tolerance. There is now a pressing need to discuss the already described and newly emerging mechanisms to see how they can be put together in a more or less cohesive structure and how they can help to improve immune response to tumors.

Suppression and Regulation of Immune Responses: Methods and Protocols (Methods in Molecular Biology)

Suppression and Regulation of Immune Responses: Methods and Protocols (Methods in Molecular Biology)
by Maria Cristina Cuturi (Editor), Ignacio Anegon (Editor)


Over the past several years, a high diversity of regulatory cells and suppressive molecules has taken centre stage in the field of immunoregulation. In Suppression and Regulation of Immune Responses: Methods and Protocols, expert researchers highlight recent advances in the identification, characterization, and generation of regulatory cells not only of the T cell lineage but also of other origins such as B, NK, myeloid, and dendritic cells, as well as the role of several suppressive molecules in immunoregulation. Particular emphasis is placed on the characterization of the molecular mechanisms and the therapeutic applications of regulatory cells and molecules in human diseases. Written as a volume in the highly successful Methods in Molecular Biology™ series, this work provides the...

Basic Immunology: Functions and Disorders of the Immune System, 4e

Basic Immunology: Functions and Disorders of the Immune System, 4e
by Abul K. Abbas MBBS (Author), Andrew H. H. Lichtman MD PhD (Author), Shiv Pillai MBBS PhD (Author)


Understand all the essential concepts in immunology with Basic Immunology: Functions and Disorders of the Immune System! This concise, focused text provides you with an up-to-date, accessible introduction to the workings of the human immune system. Efficiently master the immunology information you need through clinically focused content, logically organized by mechanism. Apply what you've learned to real-world situations by referencing the appendix of clinical cases. Enhance your learning with the help of numerous full-color illustrations and useful tables, as well as summary boxes, review questions, and a glossary of immunology terms.Study immunology anywhere! Online access to www.StudentConsult.com opens the door to an enhanced e-book and ancillary components!Visualize complex...

Immune Restoration Handbook, Second Edition

Immune Restoration Handbook, Second Edition
by Mark Konlee (Author), Conrad LeBeau (Author)


A condensed guide of information based on case reports and hands-on experience in immune-based, dietary and nutritional therapies leading to cutting-edge complementary treatments for candidiasis, CFIDS (chronic fatigue syndrome), hepatitis, HIV, HPV, EBV, HHV-6, Herpes, and cancer, including new discoveries on correcting thyroid and adrenal dysfunction and how this relates to immune function. Cell-mediated, humoral and mucosal immunity are discussed in great detail. Restore and balance the TH1/TH2 arms of the immune system; discover the cure for candidiasis and other health related conditions

A Guide to Transfer Factors and Immune System Health: 2nd edition, Helping the body heal itself by strengthening cell-mediated immunity

A Guide to Transfer Factors and Immune System Health: 2nd edition, Helping the body heal itself by strengthening cell-mediated immunity
by Aaron White PhD (Author)


In the second edition of this popular book, Dr. White takes readers on a tour of the human immune system, explores the nature of immune disorders from cancer to HIV and presents evidence that immune messengers called transfer factors can help the body beat a wide variety of diseases for which effective treatments are lacking. In language that is easy to follow, Dr. White explains how transfer factors help the body fight viruses (herpes, hepatitis C, HPV, HIV), mycobacteria (tuberculosis), cell-wall deficient bacteria (Lyme), cancers, autoimmune diseases and other conditions. Like vaccines but safer, transfer factors can be used to immunize the public against diseases before they spread. This book is an enjoyable read about a fascinating topic. As in the first edition, Dr. White blends...

Antiviral Strategies and Immune Nutrition: Against Colds, Flu, Herpes, AIDS, Hepatitis, Ebola, and Autoimmunity: A Concept-Based and Evidence-Based ... Use (Dysbiosis in Human Disease) (Volume 2)

Antiviral Strategies and Immune Nutrition: Against Colds, Flu, Herpes, AIDS, Hepatitis, Ebola, and Autoimmunity: A Concept-Based and Evidence-Based ... Use (Dysbiosis in Human Disease) (Volume 2)
by Alex Vasquez (Author)


AntiViral Strategies and Immune Nutrition provides doctors, nurses, and the general public with access to proven clinical protocols to improve immunity and fight infections, especially viral infections. This illustrated and completely re-organized outline is updated from Dr Vasquez's previous versions published in 2009 and the most recently in Rheumatology v3.5 (2014). This book provides concepts and clinical approaches cited to biomedical and clinical research in a format that is easy to access and which provides internet hyperlinks to database websites, full-text articles, instructional videos, updates, and tutorials. The digital version of the book is available for computers, tablets/iPads, and smartphones as Antiviral Nutrition (ASIN: B00OPDQG4W) and is updated regularly and provides...

© 2014 BrightSurf.com