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Old 01-23-2015, 04:21 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, 04:27 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, 04:32 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, 04:37 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, 07:34 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, 07:38 PM
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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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Old 02-03-2015, 04:05 PM
gdpawel gdpawel is offline
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Default Immunotherapy Medicines are Producing Cancer Super-Survivors

By Ed Silverman
The Wall Street Journal - Pharmalot

Meet Tom Telford, who some people call “the liver guy.”

Why? Telford, a New York City schoolteacher, may be a poster child for a growing effort to harness a new batch of drugs that are transforming the fight against cancer.

Known as immunotherapy medicines, they unleash the body’s own immune system to attack cancer and, thanks to one of these drugs, Telford is among a growing group of ‘super-survivors’ whose survival is charting new territory, according to The Wall Street Journal.

Telford and others described in the story are helping to revive hopes that the long-maligned idea of enlisting the power of the immune system against cancer may help to turn the tide against some of the most lethal and resistant forms of the disease, the paper writes.

“It’s the most exciting thing I’ve ever seen,” David Lane, scientific director at the Ludwig Institute for Cancer Research in New York, tells the Journal. “It’s the long-term survival of people who have advanced disease. This is very unusual.”

The drugs come in different forms, but those sparking the most interest are called checkpoint inhibitors. These medicines work by releasing the natural brakes on the immune system, enabling T-cells – which are the equivalent of foot soldiers – to attack tumors, the paper writes.

The field, however, is still in the early stages and, the Journal notes, more rigorous studies are needed, especially given the ability of cancer to develop resistance to different medicinal approaches. Drug makers and researchers are striving to overcome huge obstacles, as a result.

Such as? The story points out that most patients to do not respond the way Telford has and are only beginning to understand why. And there is also uncertainty why some patients relapse while remaining on therapy but others go into prolong remission after undergoing just one course of treatment.

Consider Telford. Nine years ago, he was diagnosed with Stage 4 melanoma, a skin cancer that is typically fatal within a year. The disease had spread to his kidney and liver, and he subsequently underwent chemotherapy.

In 2006, he enrolled in a study of a drug being developed by a Bristol-Myers Squibb drug and a protocol called for four treatments, one every three weeks, according to the paper. The goal was to shrink tumors in 12 weeks.

Here was the rub: although the treatment failed to work – scans showed the tumors in his liver had gotten much larger, Telford told his doc it was the best he had felt in months. “I don’t care what your scans say, I feel better,” he recalls saying to his doctor, the paper writes.

There are other examples of people who have been treated with immunotherapy drugs and you can read about them here.

[url]http://www.wsj.com/articles/cancers-super-survivors-how-immunotherapy-is-transforming-oncology-1417714379
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Old 02-05-2015, 09:42 PM
gdpawel gdpawel is offline
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Default Potential Strategy Aims To Stimulate The Immune System To Defeat Cancers

Cells have their own recycling system: discarded cellular components, from individual proteins through to whole cellular organs, are degraded and the building blocks re-used in a different place. The scientific term for this recycling process is autophagy. In severely damaged cells, autophagy can also be a form of programmed cell death.

In this case, the cell uses the mechanism for complete self-decomposition. It is assumed that highly aggressive cancer cells use autophagy to resist tumor therapy. Investigations are leading to whether blocking the recycling system (autophagy) might be useful to support anti-cancer therapies. They are bascially rediscovering something reported 20 years ago (JNCI, 83:37-42, 1991).

This study had lead to the focus on the human tumor primary culture microspheroid (microclusters) platform. The functional profiling platform studies cancer response to drugs from actual human microspheroids (tumor microenvironment), enabling it to provide clinically relevant predictions to individual cancer patients.

This is why the functional profiling platform has recognized interplay between cells, stroma, fibroblasts, vascular elements, cytokines, macrophages, lymphocytes and other extracellular material like autophagy. This had lead to the focus on the human tumor primary culture microspheroid (microclusters), which contains all of these elements.

The functional profiling platform studies cancer response to drugs (from actual human microspheroids), within this microenvironment, enabling it to provide clinically relevant predictions to individual cancer patients. It is their capacity to study "human" tumor microenvironments that distinguishes it from other platforms in the field.

"No tools exist today to measure which chemotherapy agent or combinations act by stimulating the immune system to control cancers?" Dr. Larry Weisenthal, of the Weisenthal Cancer Group, had reported on a tumor immunotherapy study back in the early 90's. It was a concept of in situ cancer vaccination based upon studies of biologic response modifiers in an assay.

Preliminary results found a striking association between the activity of biologic response modifiers which activate macrophages and the prior treatment status of patients with breast and ovarian cancers. Effective chemotherapy produced a massive release and processing of tumor antigens, which led to a state in which the human immune system, via in situ cancer vaccination, responded to exogenous macrophage activation signals with potent and specific anti-tumor effects.

Because all research was prematurely abandon back then, Dr. Weisenthal had to refocus gears and today has brought us the latest technology called Functional Tumor Cell Profiling (recently known as Personalized Cancer Cytometrics). However, one of the themes at the 2012 American Association for Cancer Research (AACR) meeting held in Chicago was the growing development of meaningfully effective immune therapies. There was evidence of a renewed interest in tissue cultures as the best platform to study drug effects and interactions.

Literature Citation:

Weisenthal LM, Dill PL, Pearson FC (1991) Effect of prior cancer chemotherapy on human tumor-specific cytotoxicity in vitro in response to immunopotentiating biologic response modifiers. J Natl Cancer Inst 83: 37-42

Weisenthal LM (1991) Effect of prior chemotherapy on biologic response modifier activity. J Natl Cancer Inst 83: 790-791

Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, et al. (2000) Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase 3 trial. Br J Cancer 82:1138-1144, 2000.

[url]http://jnci.oxfordjournals.org/content/83/1/37.short
[url]http://www.wipo.int/patentscope/search/en/WO1989003995
[url]http://www.google.com/patents?hl=en&lr=&vid=USPAT4996145&id=waMaAAAAEBAJ &oi=fnd&printsec=abstract#v=onepage&q&f=false
[url]http://www.google.com/patents?hl=en&lr=&vid=USPAT5149527&id=vO4fAAAAEBAJ &oi=fnd&dq=weisenthal+immune&printsec=abstract# v=o nepage&q=weisenthal%20immune&f=false
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Old 02-20-2015, 10:40 PM
gdpawel gdpawel is offline
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Default Immunotherapy actually works

Larry M. Weisenthal, M.D., PhD., has the patent for a laboratory-testing method that identifies cancer patients who can benefit from new drugs designed to strengthen their immune systems. The testing could make it easier to test the effectiveness of new immunotherapy drugs. He had discovered that endothelial cells (artery-forming cells) die in a special way that involves release of highly calcified micro-particles. These escape from dying endothelial cells and trigger the body's normal immune response.

Read more about it: [url]http://www.vasocell.com/MCED_Discovery.html
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Old 02-26-2015, 09:49 PM
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Default Checkpoint inhibitors/immune modulators

Alexandra Mulvey
Cancer Research Institute

Yervoy (ipilimumab), which targets the CTLA-4 checkpoint molecule on activated immune cells, has been at the vanguard of checkpoint inhibitors, and was approved to treat melanoma in 2011. Patients with melanoma got more good news in 2014, with the FDA approval of Merck’s Keytruda (pembrolizumab) and Bristol-Myers Squibb’s Opdivo (nivolumab), which target the PD-1 pathway. Several ongoing studies suggest PD-1 pathway inhibitors may benefit patients with a number of cancers, including lung, brain, head and neck, kidney, and other cancers.

Immunotherapies targeting CTLA-4 and PD-1 have gotten quite a lot of press recently. And for good reason: they are radically improving the treatment odds of many patients with cancer. But these two checkpoints are really just the beginning. There are many other checkpoint inhibitors in the drug development pipeline, and the Cancer Research Institute is leading the charge to bring them to patients.

On the Flip Side: PD-L1 Inhibitors

PD-L1, which is expressed on cancer cells and makes the immune response shut down, has been seeing positive results. One PD-L1 inhibitor is called MPDL3280A, which is being developed by Roche/Genentech and received “Breakthrough Therapy” designation from the FDA for bladder cancer in June 2014. It is in phase III testing for bladder cancer and non-small cell lung cancer, and is in phase I and II trials for melanoma, kidney cancer, lymphoma, and solid tumors. Bryan A. Irving, a 1996-1999 CRI postdoctoral fellow who joined Genentech in 2001, led studies that culminated in the generation of MPDL3280A.

Another PD-L1 antibody is called MEDI4736, and is being developed by AstraZeneca/MedImmune. Through its Clinical Accelerator program, CRI sparked an innovative deal with its developer to bring MEDI4736 to patients. It is part of the growing repertoire of promising immunotherapies available for testing in our global cancer immunotherapy clinical trials network. MEDI4737 is in clinical trials for a number of cancers, including brain, cervical, colorectal, head and neck, kidney, lung, and ovarian cancers.

Costimulatory/Coinhibitory Molecules

The quality of the immune response of T cells is controlled by costimulatory and coinhibitory signals. CTLA-4 and PD-1/PD-L1 are coinhibitory signals that put the brakes on the immune response. Costimulatory molecules, on the other hand, are designed to enhance pre-existing anti-cancer immune responses. Through its Clinical Accelerator program, CRI has access to TRX518, an anti-GITR antibody, being developed by GITR, Inc. TRX518 is designed to enhance the immune response by enabling T cells to be more effective in attacking cancer cells. It is in a phase I trial that is enrolling patients with melanoma or other solid tumors at Memorial Sloan Kettering Cancer Center, University Hospitals in Cleveland, and the Cleveland Clinic (NCT01239134). TRX518 is the first treatment of its kind ever to be tested in human cancer patients. Another GITR antibody is MK-4166, which is produced by Merck. It is in a phase I trial for solid tumors, which started in June 2014.

4-1BB, also known as CD137, is a costimulator for activated T cells. By serving as an agonist—a chemical that binds to a receptor and activates it to produce a biological response—the anti-4-1BB antibody stimulates the first wave of the anti-tumor reaction. Lieping Chen (1999-2001 CRI preclinical grant) was funded by CRI to generate an antibody against 4-1BB. He is a holder on numerous patents related to 4-1BB and its binding agents. There are two 4-1BB antibodies in development for a number of cancers: urelumab (BMS-663513), being developed by Bristol-Myers Squibb, and PF-05082566 (PF-2566), being developed by Pfizer.

Kunle Odunsi (Scientific Advisory Council member and grantee) and colleagues have demonstrated that two inhibitory molecules, PD-1 and LAG-3 (lymphocyte activation gene 3), collaborate in suppressing the anti-tumor T cell immune response. Moreover, by giving a combination of antibodies that block PD-1 and LAG-3, they could restore T cells to full function resulting in stronger anti-tumor immunity. In a phase I trial by Bristol-Myers Squibb, a LAG-3 antibody (BMS-986016) and Opdivo (nivolumab) are being tested in patients with solid cancers. They are enrolling at the University of Chicago under Thomas Gajewski (1998-2002 investigator award and CRI Scientific Advisory Council member), Johns Hopkins University under Charles Drake (predoctoral sponsor and SAC member), Dana-Farber Cancer Institute under F. Stephen Hodi (clinical trials network member), and Memorial Sloan Kettering Cancer Center under Margaret Callahan (2012-2014 CRI postdoctoral fellow) (NCT01968109).

Timothy N.J. Bullock (2005-2010 CRI investigator award), at the University of Virginia Health System, showed that a monoclonal antibody designed to activate the CD27 costimulatory molecule—which plays an important role in the activation, survival, and differentiation of T cells—caused substantial reduction in the progression of lung metastases and primary tumors in a model of melanoma. An agonist anti-CD27 antibody is being developed by Celldex, under the name varlilumab (CDX-1127). It is being tested in a phase I trial for CD27-expressing B cell cancers, any T cell cancer, and solid tumors, including melanoma, kidney cancer, prostate cancer, ovarian cancer, colorectal cancer, and lung cancer. It is also being tested with the vaccine ONT-10, which targets the MUC1 antigen, in breast and ovarian cancers.

CD40 was originally discovered by Edward A. Clark (1978-1980 postdoctoral fellow) and Jeffrey Ledbetter, as an activating protein on the surface of B cells[i]. The CD40 pathway is now understood to activate dendritic cells and license them to promote CD8+ T cell activation and proliferation. A number of clinical trials testing CD40 agonists as an immunotherapy for cancer are complete. One being studied is CP-870,893, being developed by Pfizer. In a phase I clinical trial, Gregory L. Beatty (2013-2017 CRI grantee, pictured left) and Robert H. Vonderheide (Scientific Advisory Council member) treated 21 patients with pancreatic cancer, and got a partial response in five. A phase II study is being planned.

There are many more checkpoint inhibitors/immune modulators in the pipeline—OX40, TIM-3, ICOS, BTLA, and more. Their combination will soon transform the treatment of many if not all types of cancer. Give today to help CRI continue to fund breakthrough research that is revolutionizing cancer treatment.

[i] Clark EA, Ledbetter JA. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci U S A 1986; 83: 4494–8. (PMID: 3487090)
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