TAG: "Cancer"

Stem cell science takes bold step at UC San Diego


Three first-in-human clinical trials are underway.

A 26-year-old woman paralyzed after a motor vehicle accident a year ago has successfully undergone a first-in-human experimental procedure to test whether neural stem cells injected at the site of a spinal cord injury is safe and could be an effective treatment.

The procedure, conducted on Sept. 30 under the auspices of the Sanford Stem Cell Clinical Center at UC San Diego Health System and in collaboration with Neuralstem Inc., a Maryland-based biotechnology firm, is the first of four in the phase one clinical trial. Post safety testing, it’s hoped that the transplanted neural stem cells will develop into new neurons that bridge the gap created by the injury, replace severed or lost nerve connections and restore at least some motor and sensory function.

The patient, whose identity remains confidential for privacy reasons, has been discharged and is recovering without complication or adverse effects at home, said Joseph Ciacci, M.D., principal investigator and neurosurgeon at UC San Diego Health System.

The spinal cord injury trial is one of three recent groundbreaking stem cell efforts at UC San Diego, supported by the Sanford Stem Cell Clinical Center, to make the significant leap from laboratory to first-in-human clinical trials.

Last month, researchers at UC San Diego Moores Cancer Center and the Sanford Stem Cell Clinical Center launched a novel phase one trial to assess the safety of a monoclonal antibody treatment that targets cancer stem cells in patients with chronic lymphocytic leukemia, the most common form of blood cancer.

And later this month, the first patient is scheduled to receive an unprecedented stem cell-based therapy designed to treat type 1diabetes in another phase one clinical trial at UC San Diego.

“What we are seeing after years of work is the rubber hitting the road,” said Lawrence Goldstein, Ph.D., director of the UC San Diego Stem Cell program and Sanford Stem Cell Clinical Center at UC San Diego Health System. “These are three very ambitious and innovative trials. Each followed a different development path; each addresses a very different disease or condition. It speaks to the maturation of stem cell science that we’ve gotten to the point of testing these very real medical applications in people.”

To be sure, Goldstein said, the number of patients involved in these first trials is small. The initial focus is upon treatment with low doses to assess safety, but also with hope of patient benefit. As these trials progress – and additional trials are launched – Goldstein predicts greater numbers of patients will be enrolled at UC San Diego and the Sanford Stem Cell Clinical Center and elsewhere.

“Clinical trials are the safest way to pursue potential therapies. You want to prove that a new therapy will work for more than just a single, random patient.”

While stem cell-based trials are beginning to emerge around the country, Goldstein noted that San Diego continues to assert itself as a stem cell research hub and a leading force for translating basic discoveries into medical applications, now and in the future.

“These innovative trials are the result of some truly rare features you find at UC San Diego and in the region,” he said. “There is a unique sense of collaboration and communication here among scientists in academia, clinical medicine and the biotechnology industry. An enterprise like the Sanford Center can promote and accelerate the very complex processes of research, development and testing so that the right people make the right connections and the right ideas and trials get fast-tracked, but in a way that ensures fundamentally the safety of patients while striving for benefit.”

More about the three trials:

Neural stem cell transplants and spinal cord injuries
The Neuralstem phase one clinical trial, conducted over five years with four patients, is designed to assess the safety and efficacy of an approach that might, it is hoped, someday be a treatment for paralyzing spinal cord injuries.

In preclinical studies, Ciacci and Martin Marsala, M.D., a professor in the Department of Anesthesiology at UC San Diego School of Medicine and the Sanford Consortium for Regenerative Medicine, and colleagues grafted human neural stem cells into rats with spinal cord injuries. The introduced cells showed extensive growth and connected to remaining nerve cells near the injury site, resulting in significantly improved motor function with minimal side effects in animal models.

The goal now is to determine whether similar effects occur in human patients. The researchers will also test for possible therapeutic benefits, such as reduced paralysis and improvements in motor and sensory function, bowel and bladder function and pain levels.

VC-01 and Type 1 diabetes
In collaboration with ViaCyte Inc., a San Diego-based biotechnology firm specializing in regenerative medicine, UC San Diego researchers led by principal investigator Robert Henry, M.D., professor of medicine in the Division of Endocrinology and Metabolism at UC San Diego and chief of the Section of Endocrinology, Metabolism & Diabetes at the Veterans Affairs San Diego Healthcare System, have launched the first-ever phase one-two clinical trial of a stem cell-derived therapy for patients with Type 1 diabetes. The first procedure is planned for later this month, with a second tentatively scheduled in mid-November.

Type 1 diabetes mellitus is a life-threatening chronic condition in which the pancreas produces little or no insulin, a hormone needed to allow glucose to enter cells to produce energy. It is typically diagnosed during childhood or adolescence, but can also strike adults. Though far less common than Type 2 diabetes, which occurs when the body becomes resistant to insulin, Type 1 may affect up to 3 million Americans with emotionally and financially devastating consequences. Standard treatment involves daily injections of insulin and rigorous management of diet and lifestyle. Currently, there is no cure.

The two-year trial will involve approximately 40 study participants at four to six testing sites, with San Diego being first. The trial will assess the safety, tolerability and efficacy of varying doses of VC-01, which involves implanting specially encapsulated embryonic stem cell-derived cells under the skin of patients where it’s hoped they will safely mature into pancreatic beta and other cells able to produce a continuous supply of needed insulin and other substances.

Development and testing of VC-01 is funded, in part, by the California Institute for Regenerative Medicine (CIRM), Sanford Stem Cell Clinical Center and JDRF, formerly known as the Juvenile Diabetes Research Foundation. Clinical testing and coordination is provided by UC San Diego Clinical and Translational Research Institute.

Cirmtuzumab and leukemia
Researchers at UC San Diego Moores Cancer Center and the Sanford Stem Cell Clinical Center have launched a phase one human clinical trial to assess the safety and efficacy of a new monoclonal antibody for patients with chronic lymphocytic leukemia (CLL), the most common form of blood cancer in adults.

The drug, called cirmtuzumab, targets a molecule called ROR1 that normally is used only by embryonic cells during early development, but which is abnormally exploited by cancer cells to promote tumor growth and spread, otherwise known as metastasis. Metastasis is responsible for 90 percent of all cancer-related deaths.

Because ROR1 is not used by normal adult cells, scientists believe it is a unique marker of cancer cells in general and cancer stem cells in particular. ROR1 appears to drive tumor growth and disease spread and scientists think that presents an excellent novel target for anti-cancer therapy.

Cirmtuzumab was developed at Moores Cancer Center in the laboratory of Thomas Kipps, M.D., Ph.D., who led this effort as one of six projects initially funded through CIRM’s HALT leukemia grant to co-principal investigators Dennis Carson, M.D., and Catriona Jamieson, M.D., Ph.D.  The drug’s name acknowledges CIRM’s continued support in a “Disease Team III” award, which provides some of the resources needed for a clinical trial. The Leukemia and Lymphoma Society has also provided additional support.

The trial will involve patients with relapsed or refractory CLL receiving an intravenous infusion every 14 days at Moores Cancer Center, followed by regular monitoring and clinic visits to assess efficacy and identify and manage any adverse effects. Initial treatment is planned for two months.

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New target ID’d for personalized brain cancer treatment


UC San Diego finding focuses on a fusion protein.

Clark Chen, UC San Diego

Researchers at the UC San Diego School of Medicine have identified a new fusion protein found in approximately 15 percent of secondary glioblastomas or brain tumors. The finding offers new insights into the cause of this cancer and provides a therapeutic target for personalized oncologic care. The findings were published this month in the online edition of Genome Research.

Glioblastoma is the most common and deadliest form of brain cancer. The majority of these tumors – known as primary glioblastomas – occur in the elderly without evidence of a less malignant precursor. Secondary glioblastomas occur mostly in younger patients and progress from low-grade, less aggressive precursor tumors to glioblastoma, the most aggressive form of the disease.

“While genomic profiling is yielding improved understanding of primary glioblastoma, our understanding of secondary glioblastoma remains rudimentary,” said Clark Chen, M.D., Ph.D., vice chairman of research and academic development, Division of Neurosurgery, UC San Diego School of Medicine and a principal investigator of the study. “In this study, we used a technology called RNA-Seq to study the RNA sequences derived from 272 clinical tumor specimens from patients afflicted with secondary glioblastoma or precursor forms of this tumor.”

The study revealed that the RNA sequences of brain cancers become progressively more abnormal as the tumor become more malignant. Specifically, the frequency of aberrant RNAs fusing gene sequences not normally found next to one another increased with tumor grade. Most of these fusion junctions occur in seemingly random locations. However, transcripts involving fusions of the PTPRZ and MET gene were found repeatedly in clinical specimens derived from different patients. The study estimates that 15 percent of the secondary glioblastoma harbor this fusion.

“The recurrent nature of this fusion transcript suggests that the fusion did not arise by chance. Instead, it’s likely that the fusion actively contributes to the biologic behavior of the tumor,” said Chen, who collaborates with a multidisciplinary team at UC San Diego Moores Cancer Center. “Supporting this hypothesis, we demonstrated that glioblastoma cells expressing the PTPRZ-MET fusion are more invasive and patients afflicted with these tumors showed particularly poor survival relative to other secondary glioblastoma patients.”

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NCI grant awarded to study novel cancer treatment


UC Davis will study combining a novel type of immunotherapy with radiation, chemotherapy.

Robert Canter, UC Davis

A multidisciplinary team at UC Davis will embark on research to determine whether combining a novel type of immunotherapy with radiation and chemotherapy can make treatment for sarcoma, breast and pancreatic cancers more effective.

The work is funded with a $1.7 million, 5-year grant from the National Cancer Institute (NCI) and will involve the UC Davis Laboratory of Cancer Immunology in the Department of Dermatology, Division of Surgical Oncology, Department of Radiation Oncology, as well as the School of Veterinary Medicine.

“We think we have a novel and potentially high-impact treatment that can be developed fairly rapidly for clinical use,” said Robert Canter, associate professor of surgical oncology and a lead researcher on the project. The treatment would combine an immune therapy derived from natural killer cells with traditional drug and radiation therapy.

Sarcoma, breast and pancreas cancers were chosen for the study because they can be aggressive and difficult to treat, and they lend themselves to an approach in which tumor specimens can be examined before and after treatment to determine their efficacy, he said.

Impetus for the study comes from earlier research demonstrating the importance of natural killer cells, which develop in the bone marrow, in helping prevent relapse in patients who undergo stem cell transplants for treatment of leukemia and other diseases. Studies have shown that natural killer cells are important to the body’s natural defenses against virally-infected and malignant cells, and they help to regulate immune cell function.

“We know from studies in bone marrow transplantation that natural killer cells reject hematopoietic stem cells and prevent bone marrow engraftment, so we have hypothesized that natural killer cells can also target cancer stem cells, since there are similarities and shared properties between the hematopoietic stem cells and cancer stem cells,” Canter explained.

Because they are resistant to chemotherapy and radiation therapy, cancer stem cells can repopulate after treatment, causing relapses and cancer spread. The UC Davis researchers will use natural killer cells as a form of immune therapy to attack cancer stem cells.

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New melanoma drug therapy improves survival rate


Combining Zelboraf with cobimetinib also shows a decreased risk of secondary cancers.

Antoni Ribas, UCLA

A researcher at UCLA’s Jonsson Comprehensive Cancer Center has helped develop a combination drug therapy that shows promise in extending the lives of people with metastatic melanoma. This new therapy also accomplishes this without the side effect of a secondary skin cancer seen in some patients prescribed only one of the drugs.

An estimated 70,000 new cases of melanoma are diagnosed each year in the United States. Of those, 8,000 people will eventually die of the disease, when the cancer spreads to other parts of their bodies. About half the people with this metastatic melanoma, or 4,000 people a year, have a mutated protein called BRAF mutation.

In the new study co-authored by Dr. Antoni Ribas, UCLA professor of medicine and a member of the Jonsson Cancer Center, researchers found that the BRAF mutation gives melanoma the signal to grow continuously as a cancer.

This mutation can be treated with the recently FDA-approved drug Zelboraf. But Zelboraf taken by itself  cannot completely block that signal. The study showed that when the experimental drug cobimetinib is added, the combination slows the growth of the melanoma.

The study was published online by The New England Journal of Medicine, and will appear in its November print edition.

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UCSF researcher wins Burkitt Medal


John Ziegler recognized for his “integrity, compassion and dedication.”

Paul Browne, Trinity College Dublin’s dean of the School of Medicine, left, congratulates John Ziegler for winning the 2014 Burkitt Medal. (Photo courtesy of Trinity College Dublin)

UC San Francisco’s John Ziegler, M.D., M.Sc., has won the 2014 Burkitt Medal, an award given by Trinity College Dublin to recognize people who embody “integrity, compassion and dedication,” similar to characteristics of Denis Burkitt, a Trinity alumnus.

“Dr. Ziegler has made significant contributions to the fields of medical oncology and to global health,” said Owen Smith, professor of medicine and hematology at Trinity College Dublin. “Continuing the legacy of Denis Burkitt, (Ziegler) directed a highly productive research team in Uganda that made dramatic progress to cure a particularly lethal form of childhood cancer. Ziegler’s career amply exemplifies Burkitt’s curiosity, leadership and humanity.”

The Burkitt Medal was presented at a celebratory dinner on Sept. 17 as part of the Ninth International Cancer Conference at Trinity College Dublin.

“I was delighted to be selected for this prestigious award from one of the oldest universities in Europe,” said Ziegler, founding director of Global Health Sciences Graduates Programs Education & Training at UCSF. “Denis Burkitt was my mentor in the early years of my medical career in Uganda. Receiving the Burkitt medal is a great honor.”

Burkitt discovered a cancer of the lymphatic system in 1956 among children in Africa. The disease starts in immune cells called B-cells and is one of the fastest growing human tumors. It can be fatal if left untreated.

“His discovery of Burkitt’s lymphoma opened many doors in cancer research: viral oncogenesis, tumor immunity and, most importantly, the potential for cure with chemotherapy,” Ziegler said. “Burkitt went on to advocate the importance of dietary fiber in health. He was one of my heroes in medicine.”

Leaders at Trinity praise Ziegler and his contributions to the field of cancer research.

“Burkitt’s legacy, celebrated at this event, is continued by Dr. John Ziegler,” said Paul Browne, Trinity College Dublin’s dean of the School of Medicine. “Ziegler’s work on cancer, especially in connection with developing countries, is tremendous.”

Guests from Canada, the United States, Great Britain, Germany, France, Malta, Malaysia and Ireland who were participating in the International Cancer Conference attended the event.

Ziegler received his bachelor’s degree in English Literature from Amherst College, in Amherst, Massachusetts, and his M.D. from Cornell University Medical School in New York City. Following medical house staff training at Bellevue Hospital in New York, he joined the National Cancer Institute (NCI) in 1966, beginning a life-long career in cancer research and care. In 1967 he was assigned to begin a long collaboration with Makerere University in Kampala, Uganda, studying Burkitt’s lymphoma and other indigenous cancers. Together with Ugandan counterparts, he developed curative therapies for lymphoma and established a cancer institute that today has expanded to a major center of excellence in sub Saharan Africa.

After five years Ziegler returned to NCI to head clinical oncology, and in 1981 moved to UCSF. The AIDS pandemic made its first appearance in San Francisco, heralded by opportunistic infections and two malignancies: Kaposi’s sarcoma and non Hodgkin’s lymphoma. Ziegler and colleagues made important contributions to this field both in California and back in Uganda. In his later career, earning an M.Sc. in epidemiology from the London School of Hygiene and Tropical Medicine, Ziegler headed a cancer genetics clinic at UCSF, and most recently was founding director of a global health master’s degree.

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Brain Innovation Group funded for brain tumor tool


National Cancer Institute grant boosts development of optical wand technology.

Laura Marcu, UC Davis

The UC Davis Comprehensive Cancer Center’s Brain Innovation Group has received a grant from the National Cancer Institute (NCI) to improve brain cancer surgery and treatment using UC Davis-developed biophotonic technology.

The $400,000 grant is the first for the cancer center’s eight cancer research innovation groups, which link scientists, oncologists, surgeons, engineers and other experts in discussions about patient care needs and potential innovations.

“The groups were started to fulfill a big part of our mission as a comprehensive cancer center by enhancing clinical and translational cancer research,” said cancer center director Ralph de Vere White. “This grant is a clear example of the success of this endeavor.”

UC Davis researchers will use the funding to adapt state-of-the-art optical biopsy technology, the Multispectral Scanning-Time Resolved Fluorescence Spectroscopy, to help neurosurgeons distinguish between radiation necrosis and cancer recurrence during brain cancer surgery. The technology was developed by Laura Marcu, professor of biomedical engineering and neurological surgery and principal investigator on the project.

The collaborative Brain Innovation Group includes specialists from adult and pediatric oncology, neurology, neurosurgery, neuroradiology, radiation oncology, biomedical engineering and biophotonics, hematology and biochemistry. They meet once a month in an open forum to present their projects and look for ways to combine and translate their work into high-impact clinical trials.

“This NCI grant demonstrates the benefit of having experts with different backgrounds work together to find new ways to better diagnose and treat cancer,” said Marcu, adding that the idea to apply the novel photonic technology in distinguishing between brain tumor recurrence and radiation necrosis was sparked during an innovation meeting.

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Teens help family of girl with liver cancer


Westside teens ‘aiming to do good wherever good can be done’ aid UCLA patient, her family.

David Mezquita kisses his 4-year-old daughter Vicky, who has liver cancer and is undergoing treatment at Reagan UCLA Medical Center. To help the family pay for nursing care, an organization of Westside teenagers raised money through a garage sale.

When Myra and David Mezquita of the South Bay had triplets, they knew they were blessed even though they had their hands more than full caring for the new arrivals as well as their teenagers.

Then one of the triplets, Vicky, was diagnosed with liver cancer and needed a transplant, which was performed at UCLA in April 2013 by Dr. Ronald Busuttil, distinguished professor and executive chairman of the UCLA Department of Surgery. Things seemed to be going well at first. But sadly, less than a year later, Vicky was diagnosed with recurrent cancer in her new liver.

To eradicate some liver tumors that remained unaffected by the chemotherapy, the 4-year-old underwent chemotherapy and stereotactic body radiation therapy (SBRT), a newer radiation treatment that noninvasively focuses high doses of radiation to kill tumors in a few treatment sessions.

The Mezquitas were juggling treatment appointments and caring for their other children when they lost crucial supplemental funding they had used to pay for nursing care for Vicky. Piling onto the family’s troubles, a utility-sparked fire that occurred about the time of Vicky’s transplant destroyed their backyard, including all the fencing and landscaping, leaving the children no safe place to play. Because of Vicky’s need for intense care following the transplant, no repairs were ever made, said her mother Myra Mezquita.

Members of Teamwork Makes the Dream Work join medical staff and family members at Vicky Mezquita's bedside in Reagan UCLA Medical Center.

Fortunately, some Westside teens who raise money to help sick children through a charity they co-founded, Teamwork Makes the Dream Work, found out about the family’s plight. Guided by the organization’s motto, “Aiming to do good wherever good can be done,” they held their annual garage sale and raised more than $5,100 for Vicky’s family, money that will help them augment her nursing care and create a new backyard for Vicky and her siblings to enjoy.

“We went all over the Westside, from Santa Monica to West Hollywood, gathering donations for the garage sale,” group member Nahal Shakib, 19, of Pacific Palisades said. “It was really important to us to raise a lot of money.”

Shakib and three members from Brentwood — Jasmine Shaouli, 18; Leila Aframian, 17; and Devon Shalom, 17 —  recently presented a check to David Mezquita, who was visiting his daughter while she was in Reagan UCLA Medical Center because of a low white blood cell count caused by the chemotherapy. The teens also brought gifts for Vicky’s siblings as well.

Dr. Julie Kang, a resident in the Department of Radiation Oncology, was able to connect the teens with the Mezquita family through a mutual friend. Kang was there when the check and gifts were presented to the family, along with Vicky’s radiation oncologist, Dr. Percy Lee, who oversaw the radiation treatments, and nurse Adriana Grandpre-Aguiar, who assisted with her care.

“It takes a lot of help to make good things happen,” the grateful father said. “I’m very happy and pleased that everyone joined together as a team to make this happen. I’m very touched.”

Myra Mezquita said that, at times, the circumstances her family is dealing with are “beyond imaginable. I can’t express the magnitude of our gratitude for the support we received from everyone.”

Lee, an associate professor of radiation oncology and director of UCLA’s SBRT program, said he was pleased they were able to treat all the visible cancer with the new radiation therapy. “This little girl has been through a lot in the last four years, and we are hopeful that the treatments give her a fighting chance,” he said.

Lee added that he was glad the family was getting some financial assistance. Even with their money woes, he said, the Mezquita family had recently given him a thoughtful gift card to pay for his lunch at a local eatery.

Kang said it was difficult watching the Mezquitas guide their child through a second bout of liver cancer.

“Parents can sometimes feel so alone in this big battle,” she said. “It’s beyond amazing that these angels came out of nowhere to help them out.”

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Finding a better way to track emerging cell therapies using MRIs


Technique might speed development of relevant therapies.

Cellular therapeutics – using intact cells to treat and cure disease – is a hugely promising new approach in medicine, but it is hindered by the inability of doctors and scientists to effectively track the movements, destination and persistence of these cells in patients without resorting to invasive procedures, like tissue sampling.

In a paper published Sept. 17 in the online journal Magnetic Resonance in Medicine, researchers at the UC San Diego School of Medicine, University of Pittsburgh and elsewhere describe the first human tests of using a perfluorocarbon (PFC) tracer in combination with non-invasive magnetic resonance imaging (MRI) to track therapeutic immune cells injected into patients with colorectal cancer.

“Initially, we see this technique used for clinical trials that involve tests of new cell therapies,” said first author Eric T. Ahrens, Ph.D., professor in the Department of Radiology at UC San Diego. “Clinical development of cell therapies can be accelerated by providing feedback regarding cell motility, optimal delivery routes, individual therapeutic doses and engraftment success.”

Currently, there is no accepted way to image cells in the human body that covers a broad range of cell types and diseases. Earlier techniques have used metal ion-based vascular MRI contrast agents and radioisotopes. The former have proven difficult to differentiate in vivo; the latter raise concerns about radiation toxicity and do not provide the anatomical detail available with MRIs.

“This is the first human PFC cell tracking agent, which is a new way to do MRI cell tracking,” said Ahrens. “It’s the first example of a clinical MRI agent designed specifically for cell tracking.”

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Education matters when it comes to treating prostate cancer


UCLA study finds ‘decisional conflict’ could negatively impact quality of care.

They say knowledge is power, and a new UCLA study has shown this is definitely the case when it comes to men making the best decisions about how to treat their prostate cancer.

UCLA researchers found that men who aren’t well educated about their disease have a much more difficult time making treatment decisions. That challenge, called “decisional conflict,” could negatively impact the quality of their care and their long-term outcomes.

The study should serve as a wake-up call for physicians, who can use the findings to target men less likely to know a lot about their prostate cancer. Doctors can educate patients prior to their appointments so they’re more comfortable making treatment decisions, said the study’s first author Dr. Alan Kaplan, a resident physician in the UCLA Department of Urology.

“For prostate cancer, there is no one right answer when it comes to treatment. It comes down to the right answer for each specific patient, and that is heavily dependent on their own personal preferences,” Kaplan said. “Men in general, and specifically economically disadvantaged men, have a hard time deciding what their preferences are, how they feel about any possible complications and what the future after treatment might be like. If you don’t know anything about your disease, you’ll have a really tough time making a decision.”

The findings from the one-year study appear were published online by the peer-reviewed journal Cancer.

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Drug targeting leukemia cells enters clinical trial


Antibody developed at UC San Diego.

Researchers at the UC San Diego School of Medicine have launched a phase one human clinical trial to assess the safety and efficacy of a new monoclonal antibody for patients with chronic lymphocytic leukemia (CLL), the most common form of blood cancer in adults.

The new antibody targets ROR1, a protein used by embryonic cells during early development and exploited by cancer cells to promote tumor growth and metastasis, the latter responsible for 90 percent of all cancer-related deaths.

Because ROR1 is not expressed by normal adult cells, scientists believe it is a biomarker of cancer cells in general and cancer stem cells in particular. Because it appears to drive tumor growth and disease spread, they believe it also presents an excellent target for anti-cancer therapy.

Developed at UC San Diego Moores Cancer Center by Thomas Kipps, M.D., Ph.D., who holds the Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues, the antibody is called cirmtuzumab (also known as UC-961). In previous animal studies, Kipps’ team reported that ROR1 is singularly expressed on CLL and also on a variety of different cancers, including cancers of the breast, pancreas, colon, lung and ovary. In mouse models of CLL, ROR1 acts as an accelerant when combined with another oncogene to produce a faster-growing, more aggressive cancer.

Cirmtuzumab was developed under the auspices of the California Institute for Regenerative Medicine’s HALT leukemia grant awarded to Dennis Carson, M.D., principal investigator, and Catriona Jamieson, M.D., Ph.D., co-principal investigator to develop six distinct therapies against cancer stem cells. Kipps led one of the six projects and generated antibodies against ROR1, leading to the cirmtuzumab trial in patients with CLL.

“The primary goal of this phase one clinical trial is to evaluate whether cirmtuzumab is a safe and well-tolerated cancer stem cell-targeted agent in patients with CLL,” said Jamieson, chief of the Division of Regenerative Medicine, associate professor of medicine, director of stem cell research at UC San Diego Moores Cancer Center, deputy director of the Sanford Stem Cell Clinical Center and a principal investigator of the cirmtuzumab clinical trial.

Michael Choi, M.D., assistant clinical professor of medicine and co-principal investigator of the clinical trial said, “The trial will involve patients with relapsed or refractory CLL, who will receive an intravenous infusion every 14 days at Moores, followed by regular monitoring and clinic visits to assess efficacy and identify and manage any adverse effects. Initial treatment is planned for two months.”

To learn more about eligibility for this clinical trial, call Reilly L. Kidwell at (858) 534-4801 or Samuel Zhang at (858) 534-8127.

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Cancer and immune system: A double-edged sword


Findings have importance for desigining clinical trials with drugs that target immune system.

During cancer development, tumor cells decorate their surfaces with sugar compounds called glycans that are different from those found on normal, healthy cells. In today’s (Sept. 15) online early edition of the Proceedings of the National Academy of Sciences (PNAS), researchers at the UC San Diego School of Medicine report that sialic acids at the tips of these cancer cell glycans are capable of engaging with immune system cells and changing the latter’s response to the tumor – for good and bad.

“These cell surface glycans can promote or inhibit cancer progression, depending upon the stage of the disease,” said principal investigator Ajit Varki, M.D., Distinguished Professor of Medicine and Cellular and Molecular Medicine. “Our findings underscore the complexity of cancer and the consequent challenges in conquering it. The immune system may be a double-edged sword in cancer, tumor-promoting or tumor-inhibiting, depending upon circumstances.”

Specifically, the researchers found that receptors called siglecs on subsets of neutrophils and macrophages (two types of immune cell) can bind to sialic acids on the surface of tumor cells. Depending upon the stage of cancer and the tumor model used, the scientists reported that interaction between immune cell siglecs and tumor cell sialic acids produced opposite outcomes.

“During initial stages of growth, cancer cells appear to protect themselves from extermination by neutrophils by engaging siglecs via sialic acid-capped glycans,” said Varki, who is also a faculty member of the UC San Diego Moores Cancer Center. “But once the tumor was established, further growth was inhibited by engagement of siglecs on macrophages.”

The findings follow upon research by Varki and colleagues published earlier this year in PNAS that showed anti-tumor antibodies also behave contrarily. Low concentrations of antibodies can support cancer growth, but higher concentrations may inhibit it.

“The fact that the immune system can exert a promoting or inhibiting effect on cancer progression, depending on the situation and stage of disease, has importance for designing clinical trials with drugs that target the immune system,” said first author Heinz Läubli, M.D., Ph.D.

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Targeted leukemia treatment shows promise


UC Davis develops unique treatment approach.

Noriko Satake, UC Davis

Noriko Satake, UC Davis pediatric oncologist and researcher, has demonstrated in laboratory studies that a new, targeted treatment for leukemia is effective.

Satake’s research was published Sept. 9 in the British Journal of Haematology.

“We identified a novel molecular target that is important for the growth of precursor B-cell acute lymphoblastic leukemia (ALL), the most common cancer in children,” Satake said. “We developed a unique treatment approach using a drug that blocks the target molecule and kills leukemia cells, a nanoparticle vehicle that carries the drug, and an antibody driver that delivers the nanocomplexes (drug-loaded nanoparticles) to leukemia cells.

“We showed great efficacy of these new drug nanocomplexes on a cell line and on primary leukemia samples,” she added. “We also demonstrated that they had minimal toxicities on normal blood cells.”

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