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Old 01-23-2015, 03:21 PM
gdpawel gdpawel is offline
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Default Training the immune system to fight cancer

The potential to harness the body's immune system to fight cancer may finally prove itself on a large scale in the next couple of years. Scores of new immunotherapy vaccines and other immune system modifiers are being tested against a variety of cancers. At least a dozen therapies are set to have key late- or mid-stage trial data.

The concept of using the immune system against cancer dates back to the 1890s when Dr. William Coley, a New York surgeon, noted that some patients who got infections after cancer surgery fared better. He surmised that the immune response triggered by the infection was also working to eradicate cancer.

According to Dr. Glenn Dranoff, co-director of the Dana-Farber Cancer Vaccine Center in Boston, although the idea of a vaccine or cancer immunotherapy has been around really for at least 100 years, we now know a lot more about what are the requirements to generate an effective anti-cancer immune response than we ever did.

Researchers had previously believed that only melanoma and kidney cancer had the right properties to respond to immune system therapy. They were eventually proven wrong. Clinical trials now are taking on lung, breast, liver, prostate, pancreatic, ovarian, head and neck and brain cancers.

The basic idea remains the same: train a patient's immune system to attack the cancer. But new approaches based on more recent knowledge of the immune system's components include activating a variety of cells to go after tumors and modifying mechanisms that keep either the immune system in check or turn it loose.

There appears to be near universal agreement that to achieve optimal benefit, immunotherapies should be combined with targeted cancer drugs or other immunotherapies in a multi-pronged attack.

According to the researchers at Anderson, our immune cells are like little tanks that travel round the body to shoot bacteria and viruses that are hurting us, but you can't let them go unregulated. When the body has cancer you want the tanks to go a little bit wild, so they want to lift those brakes and let them go after the enemy.

Some believe that companies would do well to test immunotherapies at an earlier stage of the disease, perhaps to prevent recurrence. Such trials take years longer to produce results, so companies tend to start trials with advanced cancer patients with limited life expectancy that yield results sooner.

The body's immune system is constantly trying to keep tumors from forming or coming back. If you can give the immune system a boost in terms of helping out with that long-term surveillance, it could make more sense biologically.

The immune system may take some months to ratchet up its anti-cancer armaments researchers say, so giving immunotherapy to a patient with just a few months to live may be futile.

Early disappointment in the field may have been due to testing on patients with very advanced disease whose immune systems were severely compromised by chemotherapy and radiation, and such failures are to be expected.
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Old 01-23-2015, 03:27 PM
gdpawel gdpawel is offline
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Default The Revival of Cancer Immunotherapy

An old idea for treating cancer is yielding impressive results on cancer patients—and lots of attention from drug companies.

New medicines that shrink tumors and have beneficial effects lasting for months to years in some cancer patients are helping breathe new life into an old idea: using a patient’s own immune cells to attack malignant cells.

Several drug makers are trying to prove the safety and efficacy of new medicines that harness the body’s own lines of defense. Merck, for one, is testing an immune-modulating compound in patients with metastatic, or spreading, melanoma. In an early-stage trial, half of the patients receiving the highest-attempted dose of the drug saw their tumors shrink or disappear, and more than a year later, the vast majority of those patients who responded to that dose and lower doses were still alive. On average, the prognosis for survival a patient with late-stage metastatic melanoma is less than a year.

“This is not a garden-variety cancer treatment development program,” says Roger Perlmutter, an immunologist who heads R&D at Merck. “This looks special at this stage,” he says.

Merck’s compound is an antibody, a Y-shaped biological molecule that grabs onto a specific protein. The target protein normally prevents immune cells from attacking cancer. By blocking the activity of that protein, the antibody frees the immune cell to fight the disease. Roche, GlaxoSmithKline, Bristol-Myers Squibb, and others are also developing antibodies to release such brakes on the immune system.

New details of how these compounds work and for whom will be presented by many groups involved in the new push for cancer immunotherapy at this year’s American Association for Cancer Research meeting, in San Diego. The conference, which started on Saturday, is the largest meeting of oncologists and oncology researchers in the world. Although researchers express excitement about the potential for immune-modulating medicines to combat cancer—some experts even use the word “cure”—many caution that it will take time to fully understand how well the treatments are working.

Just a few years ago, many in the biomedical community would have been skeptical. Numerous attempts to induce the immune system to attack cancer had proved ineffective in humans, says Charles Link, CEO of New Link Genetics, a biotech company that has been developing immunotherapies for years. “But as the sophistication of our understanding of immunology increased, new strategies evolved to attack the disease, and those strategies are turning out to work in the clinic,” says Link.

“It is exciting—we have been working on this for so long, and now finally human results show it clearly works,” says Jianzhu Chen, a biologist at the Koch Institute for Integrative Cancer Research at MIT, who studies cancer immunotherapy. “This will have a major impact on cancer treatment.”

In 2011, Bristol-Myers Squibb began to sell Yervoy, also an antibody, which was the first marketed medicine to disrupt the process that prevents immune cells from attacking cancer. The treatment has shown to nearly double the survival rate of metastatic melanoma patients, enabling 20 percent of patients to live up to four years after diagnosis. The clinical trial of Yervoy was the first ever to show that life could be extended for advanced melanoma patients.

The antibody medicines represent just one part of the renaissance of cancer immunotherapy. There’s also been progress in a form of cellular therapy that engineers a patient’s own immune cells to better recognize cancer cells, after which they are infused back into the patient. Other companies, such as Amgen, are developing virus-based gene therapies that selectively kill cancer cells while simultaneously making the cells better targets for the immune system.

The immune system can be a powerful ally for doctors, but they must tread carefully. “We know the immune system is capable of killing any cell. If we aren’t careful, we could trigger systemic autoimmune disease of major consequences,” says Perlmutter. “We have to take advantage of the enormous potential of immune recognition and response and at same time leave ourselves in a position where we can control that activity,” he says.

So far, the treatments have been tested on only a subset of cancer types—mostly melanoma but also lung cancers and breast cancers, among others. Researchers will have to test the treatments on more cancer types to know how wide a range of malignancies they can attack, and whether certain targets, or even combination of targets, are needed. “It may be that in different tumor types, different immune modulators will have different importance,” says Deborah Law, who heads one of Merck’s biologics research units. “Combination approaches might be most effective,” she says.

Citation: The Revival of Cancer Immunotherapy. Susan Young Rojahn. MIT Technology Review. April 7, 2014
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Old 01-23-2015, 03:32 PM
gdpawel gdpawel is offline
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Default New approach to immunotherapy could increase cancer patient survival

Developing immunotherapies for cancer is challenging because of significant variability among tumors and diversity in human immune types. In a study published online in Genome Research, researchers examined the largest collection of tumor samples to date to predict patient-specific tumor mutations that may activate the patient's immune system, paving the way for more successful, personalized cancer immunotherapy.

Tumor cells accrue mutations in their DNA, and as these mutations accumulate, the cell looks less and less like part of the body and more like a foreign invader to the immune system. Cancer patients with stronger anti-tumor immune responses, mediated by T cells, are more likely to live longer. Much research has focused on strategies to harness the immune system to fight cancer; however, it has been difficult to determine the tumor mutations that activate a patient's T cells because the mutations occur sporadically, and successful activation depends on the patient's immune type (specifically, their HLA type), which varies considerably from person to person.

In this new study, the authors used a collection of over 500 tumor samples to computationally predict, using both the mutation profile and the individual's immune type, which tumor mutations are likely to be "immunogenic," causing an immune response in the patient. They found that patients with one or more immunogenic mutations had higher expression of a known T cell marker, indicative of an anti-tumor T cell response. Furthermore, these patients had higher overall survival rates than patients without immunogenic mutations, suggesting the mutations are eliciting a protective immune response.

This study highlights the "personalized nature of the tumor-immune interaction" said the lead author of the study, Robert Holt. "Cancer immunotherapy is most likely to be successful if it is personalized, that is, targeted to each individual patient's immune type and mutation profile." With the decreasing cost of DNA sequencing, "it is now feasible to map these mutational profiles and design individual vaccines in relatively short order," Holt said.

Furthermore, the study demonstrates that tumors harboring large numbers of mutations are more likely to benefit from cancer immunotherapy, because they are more likely to have mutations that make the tumor susceptible to the immune system.

Holt added, "these results also support an entirely new approach to immunotherapy: creating personalized cancer vaccines that use tumor-specific immunogenic mutations to enhance anti-tumor immunity." The team is now looking to apply this strategy in combination with conventional cancer therapies.

The data in this study was generated by The Cancer Genome Atlas (TCGA), a comprehensive resource of genomic information from a large number of patient samples, funded by the U.S. National Institutes of Health.

Scientists from BC Cancer Agency, University of British Columbia, University of Victoria, and Simon Fraser University contributed to this study.

This work was supported by funding from the BC Cancer Foundation, Canadian Institutes of Health Research, and the U.S. Department of Defense.

Brown SD, Warren RL, Gibb EA, Martin SD, Spinelli JJ, Nelson BH, Holt RA. 2014. Neo-antigens predicted by tumor genome meta-analysis correlate with increased patient survival. Genome Res doi: 10.1101/gr.165985.113

Citation: Cold Spring Harbor Laboratory. "New approach to immunotherapy could increase cancer patient survival." Medical News Today. MediLexicon, Intl., 1 May. 2014.
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Old 01-23-2015, 03:37 PM
gdpawel gdpawel is offline
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Default Immunological Research: A multi-faceted approach to curing disease

Animal models of human disease have been a tremendous asset to the development of cures for disease. Unfortunately, animal physiology is often not identical to human and more appropriate models are needed. Enter stem cell technology and tissue banking.

The culture of human cells, or xenotransplantation into mice with impaired immune responses provides a platform to test new drugs or culture protocols. To achieve this, an ongoing supply of human cells must be obtained and processed.

Kimera Labs sources human tissue and then processes it for research purposes.

Our group was born out of a tragedy millions of Americans are facing on a daily basis. Cancer.

Through fund raising, education, banking, research and distribution we have developed a number of tools to advance the state of health care in the oncology field.

Funding: By creating the Kimera Society Inc, we are developing a private operating foundation currently applying for 501(c)3 status with the IRS, allowing donors to target funds directly to research labs performing promising investigations.

Education: Kimera Labs and the Kimera Society supports the development of dotcure.org and cancerfocus.org.

Launched in 2006, cancerfocus.org is a patient education site and forum which allows our scientists to come directly into contact with patients that need the most concrete information available. Dotcure.org is a new intiative of the Kimera Society to crowd source research funds.

Banking: By soliciting tissues from cancer centers around the world, we are building a library of disease tissues to facilitate new drug discovery and testing in the future. Our pioneering work in cord blood banking, will bring new discoveries and uses to the rich and under-utilized cord blood cell industry.

Research: Through ongoing collaborations with the University of Miami, Johns Hopkins and other research centers, we participate in research projects for academic publications.

Distribution: As promising therapies and drugs are developed, we aid in the distribution of materials through our network of South American pharmacies and clinics.

[url]http://kimeralabs.com/

Note: Duncan Ross, PhD. (the owner of the website I've been moderating for the last seven years) has started a tumor immunotherapy service out of his lab in Miami. When anyone gets a biopsy or surgical tumor removed, they overnight it to him and then he tries to extract the T-cells and grow them against their tumors and reinject. He is working within an ambulatory center there with two surgeons.

Animal models of human disease have been a tremendous asset to the development of cures for disease. Unfortunately, animal physiology is often not identical to human and more appropriate models are needed. Enter stem cell technology and tissue banking.

Antigen and Lymphopenia-Driven Donor T-Cells

[url]http://cancerfocus.org/forum/showthread.php?t=4015
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Old 01-31-2015, 06:34 PM
gdpawel gdpawel is offline
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Default Precision Immunology: The Promise of Immunotherapy for the Treatment of Cancer

The landscape of therapeutic options for patients with cancer has changed dramatically in the last decade. Advances in understanding the role of driver mutations in mediating tumor growth and progression, coupled with the development of molecular inhibitors for defined mutations, has given rise to a new field of cancer therapy that is often termed precision medicine or precision oncology. The basic foundation of precision medicine is that each tumor in individual patients may harbor different subsets of genomic mutations. Targeted therapy can thus be designed on the basis of a knowledge of which mutations are present at any given time, and a precise and highly personalized treatment plan for each patient can be developed. Although promising, there are several barriers that limit widespread clinical adoption, including the need to collect and properly store tissue, the lack of cost-effective companion diagnostic tests, limited funding for bioinformatics infrastructure, issues related to patient accrual in clinical trials targeting highly selected subsets of patients, barriers across industry that block rational combination regimens, and the need to better understand mechanisms of drug resistance and how to monitor patients for the emergence of resistance.

[url]http://jco.ascopubs.org/content/early/2015/01/20/JCO.2014.59.6023
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Old 01-31-2015, 06:38 PM
gdpawel gdpawel is offline
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Default A New Initiative on Precision Medicine

The New England Journal of Medicine offered its take on the Precision Medicine Initiative presented during the State of the Union address.

[url]http://www.nejm.org/doi/full/10.1056/NEJMp1500523?query=featured_home&
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