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Quarta-feira, 19.08.15

ImmunoCellular signs agreement with FDA for phase 3 registrational trial of cancer immunotherapy ICT-107

GLIOBASTOMA GBM

ImmunoCellular signs agreement with FDA for phase 3 registrational trial of cancer immunotherapy ICT-107

Published on August 13, 2015 at 8:32 AM ·

ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular") (NYSE MKT: IMUC) announced today that it has reached agreement with the US Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the phase 3 registrational trial of its cancer immunotherapy ICT-107 to treat patients with newly diagnosed glioblastoma.

The phase 3 trial is designed as a randomized, double-blind, placebo-controlled study of about 400 HLA-A2 positive subjects, which will be conducted at about 120 sites in the US, Canada and the EU. The primary endpoint in the trial is overall survival, which the FDA and EU regulators have stated is the appropriate endpoint for registrational clinical studies in glioblastoma. Secondary endpoints include progression-free survival and safety, as well as overall survival in the two pre-specified MGMT subgroups. Patient enrollment is anticipated to begin in the late third quarter or early fourth quarter of 2015.

A Special Protocol Assessment is a written agreement between the sponsor company and the FDA on the design, clinical endpoints, size and statistical design of a clinical trial intended to form the primary basis of an efficacy claim in the marketing application, such as a biologic licensing application (BLA) or a new drug application (NDA). Final marketing approval depends upon the safety and efficacy results demonstrated in the phase 3 clinical program.

Andrew Gengos, ImmunoCellular's Chief Executive Officer Commented: "We are pleased to have achieved this important milestone, and think that successful completion of the SPA process adds meaningful validation to the ICT-107 phase 3 program and design, especially the use of the gold standard primary endpoint of overall survival. With this SPA in place, we think that ICT-107 is uniquely positioned in the field of immuno-oncology approaches being tested in glioblastoma. We are making significant progress toward establishing our clinical site network and obtaining the necessary institutional review board approvals. We are confident that we are on track to begin patient enrollment in the late third quarter or early fourth quarter of this year."

Source:

ImmunoCellular Therapeutics, Ltd.

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por cyto às 11:37

Quinta-feira, 23.07.15

Magnetic nanoparticles may hold key to bringing immunotherapy into successful clinical use

 

Magnetic nanoparticles may hold key to bringing immunotherapy into successful clinical use

Published on July 16, 2015 at 1:54 AM

In recent years, researchers have hotly pursued immunotherapy, a promising form of treatment that relies on harnessing and training the body's own immune system to better fight cancer and infection. Now, results of a study led by Johns Hopkins investigators suggests that a device composed of a magnetic column paired with custom-made magnetic nanoparticles may hold a key to bringing immunotherapy into widespread and successful clinical use. A summary of the research, conducted in mouse and human cells, appears online July 14 in the journal ACS Nano.

The Johns Hopkins team focused on training and rapidly multiplying immune system white blood cells known as T cells because of their potential as an effective weapon against cancer, according to Jonathan Schneck, M.D., Ph.D., a professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine's Institute for Cell Engineering. "The challenge has been to train these cells efficiently enough, and get them to divide fast enough, that we could use them as the basis of a therapy for cancer patients. We've taken a big step toward solving that problem," he says.

In a bid to simplify and streamline immune cellular therapies, Schneck, Karlo Perica, a recent M.D./Ph.D. graduate who worked in Schneck's lab, and others worked with artificial white blood cells. These so-called artificial antigen-presenting cells (aAPCs) were pioneered by Schneck's lab and have shown promise in activating laboratory animals' immune systems to attack cancer cells.

To do that, Perica explains, the aAPCs must interact with naive T cells already present in the body, awaiting instructions about which specific invader to target and battle. The aAPCs bind to specialized receptors on the T cells' surfaces and "present" them with distinctive proteins called antigens. This process activates the T cells to ward off a virus, bacteria or tumor, as well as to make more T cells.

In a previous study in mice, Schneck's team found that naive T-cells activated more effectively when multiple aAPCs bound to different receptors on the cells, and then were exposed to a magnetic field. The magnets brought the aAPCs and their receptors closer together, priming the T cells both to battle the target cancer and divide to form more activated cells.

But naive T cells are as rare in the blood as a "needle in a haystack," Perica says. Because the ultimate goal is to harvest a patient's T cells from a blood sample, then train them and expand their numbers before putting them back into the patient, Schneck's research team looked to magnets as a potential way to separate the naive T cells from others in the blood.

The team mixed blood plasma from mice and, separately, humans with magnetic aAPCs bearing antigens from tumors. They then ran the plasma through a magnetic column. The tumor-fighting T cells bound to aAPCs and stuck to the sides of the column, while other cells washed straight through and were discarded. The magnetic field of the column activated the T cells, which were then washed off into a nourishing broth, or culture, to grow and divide. After one week, their numbers had expanded by an estimated 5,000 to 10,000 times. Because numbers of these cells could be expanded quickly enough to be therapeutically useful, the approach could open the door to individualized immunotherapy treatments that rely on a patient's own cells, says Perica.

Schneck says that the use of naive T cells could make the new technique useful for more patients than another immunotherapy now being tested, which relies on other white blood cells called tumor-infiltrating lymphocytes. Those cells are already "trained" to fight cancer, and researchers have shown some success isolating some of the cells from tumors, inducing them to divide, and then transferring them back into patients. But, Schneck says, not all patients are eligible for this therapy, because not all have tumor-infiltrating lymphocytes. By contrast, all people have naive T cells, so patients with cancer could potentially benefit from the new approach whether or not they have tumor-infiltrating lymphocytes.

"The aAPCs and magnetic column together provide the foundation for simplifying and streamlining the process of generating tumor-specific T cells for use in immunotherapy," says Juan Carlos Varela, M.D., Ph.D., a former member of Schneck's laboratory who is now an assistant professor at the Medical University of South Carolina.

The researchers found that the technique also worked with a mixture of aAPCs bearing multiple antigens, which they say could help combat the problem of tumors mutating to evade the body's defenses. "We get multiple shots on the goal," Schneck says.

While the team initially tested the new method only on cancer antigens, Schneck says it could also potentially work for therapies against chronic infectious diseases, such as HIV. He says that if further testing goes well, clinical trials of the technique could begin within a year and a half.

Source:

Johns Hopkins Medicine

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por cyto às 22:49

Quinta-feira, 23.07.15

New UW-Madison study links two unrelated cancer treatments

 

New UW-Madison study links two unrelated cancer treatments

Published on July 14, 2015 at 5:10 AM 

A new study at the University of Wisconsin-Madison has linked two seemingly unrelated cancer treatments that are both now being tested in clinical trials.

One treatment is a vaccine that targets a structure on the outside of cancer cells, while the other is an altered enzyme that breaks apart RNA and causes the cell to commit suicide. The study was published July 13 in the new journal of the American Chemical Society: ACS Central Science.

The new understanding could help both approaches, says UW-Madison professor of biochemistry Ronald Raines, who has long studied ribonucleases -- enzymes that break apart RNA, a messenger with multiple roles inside the cell. In 1998, he discovered how to alter one ribonuclease to avoid its deactivation in the body. Soon thereafter, he found that the engineered ribonuclease was more toxic to cancer cells than to others.

Raines patented the advance through the Wisconsin Alumni Research Foundation and with UW-Madison chemist Laura Kiessling cofounded Quintessence Biosciences in Madison. They remain shareholders in the firm, which has licensed the patent from WARF and begun early-phase human trials with the ribonuclease at the UW Carbone Cancer Center and MD Anderson Cancer Center in Houston.

The current study began as an effort to figure out why the ribonuclease was selective for cancer cells. To identify which structure on the cell surface helped it enter the cell, Raines screened 264 structures using a specially designed chip. The winner was a carbohydrate called Globo H.

"We were surprised -- delighted -- to see that because we already knew that Globo H is an antigen that is abundant in many tumors," Raines says. Antigens are complex molecules with structures that are recognizable to proteins called antibodies. "Globo H is under development as the basis for a vaccine that will teach the immune system to recognize and kill cancer cells," he says.

Working with Samuel Danishefsky, who solved the difficult problem of synthesizing Globo H at the Memorial Sloan-Kettering Cancer Center in New York, Raines found that reducing the Globo H display on the surface made breast cancer cells less vulnerable to ribonucleases like those that Quintessence is testing. "This was exciting, as we now have a much clearer idea of how our drug candidate is working."

Biochemistry Professor John Markley aided the research with studies of the structure of the molecules in question.

The picture that emerges from the work is of ribonucleases patrolling our bodies, looking for telltales of cancer cells, Raines says. "We are working to demonstrate this surveillance more clearly in mice, but don't have direct evidence yet."

As other scientists test whether using a vaccine will start an immune attack on Globo H, Raines says, "we are probing a different type of immunity. This innate immunity does not involve the immune system. It's a way for our bodies to fight cancer without using white blood cells or antibodies, just an enzyme and a carbohydrate."

Source:

University of Wisconsin-Madison

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por cyto às 22:46

Quinta-feira, 23.07.15

Emory University immunologists identify long-lived antibody-producing cells in bone marrow

 

Emory University immunologists identify long-lived antibody-producing cells in bone marrow

Published on July 16, 2015 at 2:40 AM · 

Immunologists from Emory University have identified a distinct set of long-lived antibody-producing cells in the human bone marrow that function as an immune archive.

The cells keep a catalog of how an adult's immune system responded to infections decades ago in childhood encounters with measles or mumps viruses. The results, published Tuesday, July 14 in , could provide vaccine designers with a goalpost when aiming for long-lasting antibody production.

"If you're developing a vaccine, you want to fill up this compartment with cells that respond to your target antigen," says co-senior author F. Eun-Hyung Lee, MD, assistant professor of medicine at Emory University School of Medicine and director of Emory Healthcare's Asthma, Allergy and Immunology program.

The findings could advance investigation of autoimmune diseases such as lupus erythematosus or rheumatoid arthritis, by better defining the cells that produce auto-reactive antibodies.

Co-senior author of the Immunity paper is Iñaki Sanz, MD, professor of medicine and pediatrics, chief of the Division of Rheumatology, Mason I. Lowance Chair of Allergy and Immunology and a Georgia Research Alliance Eminent Scholar. The research was started when Lee, Sanz and colleagues were investigators at the University of Rochester Medical Center, and continued when they arrived at Emory in 2012. The first author of the paper is Jessica Halliley, MS from Rochester.

As described in part of the Immunity paper, the researchers studied 11 older individuals (aged 43 to 70) who had not been immunized against measles or mumps, but who had antibodies in their blood indicating infection by those viruses in childhood. Measles and mumps vaccines first became available in the 1960s.

Antibodies in the blood have a half-life of just a few weeks, so researchers thought these individuals had long-lived plasma cells, or white blood cells secreting antibodies, dating from the childhood infection.

Examining bone marrow samples obtained from these volunteers, researchers divided plasma cells into four different groups based on the proteins found on their surfaces. Only one group ("subset D", CD19-, CD38high, CD138+) contained the cells that produce antibodies that react with measles or mumps virus.

"I like to call this group of cells the 'historical record' of infection or vaccination," Lee says.

In contrast, cells producing anti-influenza antibodies were found spread across three of the subsets. Because study participants were likely to have been exposed to influenza by annual vaccination or infection more recently than measles or mumps, the researchers inferred that cells specific to recent exposures can reside in multiple subsets while subset D represents the long-lived plasma cells.

In separate experiments, volunteers who were vaccinated against tetanus did have some plasma cells producing anti-tetanus antibodies within three weeks in several subsets, but over time tetanus-specific plasma cells were found in subset D.

The team proved that subset D cells were exclusively responsible for producing the measles- and mumps-specific antibodies in the blood of one of the older volunteers, through proteomics and RNA sequencing techniques.

Compared with other subsets, subset D cells are more quiescent: they displayed less signs of proliferation. In addition, subset D cells have a distinct "fried egg" appearance, containing bubble-like vacuoles or lipid droplets, which are rare in bone marrow cell samples, and a tighter, more condensed nucleus than other white blood cells.

Plasma cells differ from many other cells in the body in that they undergo changes in their DNA -- specifically, their antibody genes. In the patients the researchers examined, antibody genes from subset D are much more diverse than those from other plasma cells. Lee says this finding also reflects subset D's role as an archive, which does not devote too much cellular space to any one vaccination or infection.

Source:

Emory Health Sciences

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por cyto às 22:43

Terça-feira, 21.07.15

Patients' own genetically engineered immune cells show significant success against multiple myeloma

 

Patients' own genetically engineered immune cells show significant success against multiple myeloma

Published on July 21, 2015 at 2:37 AM 

In recent years, immunotherapy has emerged as a promising treatment for certain cancers. Now this strategy, which uses patients' own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable. The results appeared in a study published online today in Nature Medicine.

Patients received an infusion of altered immune cells known as T-cells - roughly 2.4 billion of them - after undergoing a stem cell transplantation of their own stem cells. In 16 of 20 patients with advanced disease, there was a significant clinical response. The scientists found that the T-cell therapy was generally well-tolerated and that modified immune cells traveled to the bone marrow, where myeloma tumors typically are found, and showed a long-term ability to fight the tumors. Relapse was generally associated with a loss of the engineered T-cells.

"This study suggests that treatment with engineered T-cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma," says first author Aaron P. Rapoport, MD, the Gary Jobson Professor in Medical Oncology at the University of Maryland School of Medicine. "Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients."

The trial is the first published use of genetically modified T-cells for treating patients with multiple myeloma. The approach has been used to treat leukemia as well as lymphoma, according to Dr. Rapoport, who is the Director of the Blood and Marrow Transplant Program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center.

More than 77,000 people in the United States have multiple myeloma, with about 24,000 new cases diagnosed each year. Patients are treated with chemotherapy and in many cases an autologous stem cell transplant, but long-term response rates are low, and median survival is three to five years.

"The majority of patients who participated in this trial had a meaningful degree of clinical benefit," Dr. Rapoport notes. "Even patients who later relapsed after achieving a complete response to treatment or didn't have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly three years."

The research is a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine at the University of Pennsylvania and Adaptimmune, a clinical stage biopharmaceutical company which owns the core T-cell receptor technology and funded the study. Dr. Rapoport and co-authors Edward A. Stadtmauer, MD, of the University of Pennsylvania Abramson Cancer Center, and Gwendolyn K. Binder-Scholl, PhD, of Adaptimmune, contributed equally to the research. Dr. Rapoport is the study's principal investigator.

In the clinical study, patients' T-cells were engineered to express an affinity-enhanced T-cell receptor (TCR) specific for a type of tumor antigen, or protein, known as a cancer-testis antigen (CT antigen). The target CT antigens were NY-ESO-1 and LAGE-1. Up to 60 percent of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which correlates to tumor proliferation and poorer outcomes. According to Adaptimmune, the trial is the first published study of lentiviral vector mediated TCR gene expression in humans.

Of the 20 patients treated, 14 (70 percent) had a near complete or complete response three months after treatment. Median progression-free survival was 19.1 months and overall survival was 32.1 months. Two patients had a very good partial response three months post treatment. Half the patients were treated at the University of Maryland Greenebaum Cancer Center and half at the University of Pennsylvania Abramson Cancer Center. Researchers note that the response rate was better than would be expected for a standard autologous stem cell transplant. In addition, patients did not experience side effects which have been associated with another type of genetically engineered T-cells (chimeric antigen receptors, or CARS) used to treat other cancers.

The study was originally developed by Carl H. June, MD, of the University of Pennsylvania Abramson Cancer Center, and Dr. Rapoport, who have been research collaborators for 18 years.

"Multiple myeloma is a treatable but largely incurable cancer. This study reveals the promise that immunotherapy with genetically engineered T-cells holds for boosting the body's ability to attack the cancer and provide patients with better treatments and control of their disease," says E. Albert Reece, MD., PhD, MBA, vice president for medical affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. "This trial is also an excellent example of significant scientific advances that result from collaborations between academic medical institutions and private industry."

Source:

University of Maryland Medical Center

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por cyto às 18:10

Sexta-feira, 26.06.15

Vaxon Biotech receives new patent in Japan for cancer vaccine candidates

Vaxon Biotech receives new patent in Japan for cancer vaccine candidates

Published on June 22, 2015 at 9:21 AM ·

The company’s worldwide cancer vaccines patent portfolio, made up of ten patent families, now comprises 24 issued patents

Vaxon Biotech, a company specialized in anti-tumor immunotherapy, today announces that it has been granted a new patent in Japan. This patent (JP application n°2012-502822) covers a series of optimized cryptic peptides to be used in the design of the Vbx-026, a new cancer vaccine for solid tumors.

This patent gives Vaxon exclusive rights in Japan and raises its worldwide portfolio to 24 issued patents.

The patent will support the development of Vbx-026, a vaccine dedicated to the treatment of cancer patients expressing the HLA-A24 molecule. This molecule is widely expressed in the Asian population, mainly in Japan, with more than 40% of the Japanese population expressing HLA-A24. The initiation of preclinical development of the Vbx-026 vaccine is planned for 2016.

“This new patent will strengthen our position in Japan, a promising market for the development of the Vbx-026 vaccine,” said Dr. Kostas Kosmatopoulos, CEO of Vaxon Biotech. “With four cancer vaccines under development, ranging from lead optimization to phase II, we have built a strong patent portfolio and we now cover the three major HLA molecules, corresponding to around 80% of cancer patients.”

Vaxon Biotech develops therapeutic vaccines against cancer, based on its proprietary technology of optimized cryptic peptides, which are protected by ten patent families. All vaccines developed by Vaxon target universal tumor antigens and therefore have wide-ranging applications in cancer treatment.

Vx-001 and Vx-006 are already in clinical trials (Vx-001 in an ongoing randomized phase II trial in eight European countries and Vx-006 in an ongoing phase I trial). Vbx-016 has successfully completed its preclinical development and is ready to enter clinical trials and Vbx-026 is at the final stage of lead optimization.

Vx-001 and Vx-006 can be used for the treatment of patients expressing HLA-A2, the most common HLA molecule in humans (40-45% of the world population). Vx-001 and Vx-006 are fully protected by a total of 17 patents granted in Europe, the US, Canada, China and Japan. These patents belong to four patent families and cover peptide optimization technology, the products derived from this technology and their use. Six of these patents belong to INSERM/IGR and have been licensed to Vaxon Biotech, while the remaining 11 are Vaxon’s own property.

Vbx-016 can be used for the treatment of patients expressing HLA-B7, a common HLA molecule (25% of the population). Vbx-016 is already protected by three patent families. Five patents are already granted in Europe, the US, China and South Korea. Additional patents are still under review. All these patents are Vaxon’s own property.

The global market for cancer vaccines is expected to grow to $4.3 billion (€3.8 billion) by 2019, with a five-year compound annual growth rate (CAGR) of 1.3%. Technological advancements, new product launches and unmet treatment needs are predicted to drive consistent growth in this market for the foreseeable future.

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por cyto às 00:58


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