Experimental Therapy Uses Body’s Immune System to Increase Cure Rate in Neuroblastoma Patients

A multicenter research team has announced encouraging results for an experimental therapy using elements of the body’s immune system to improve cure rates for children with neuroblastoma, a challenging cancer of the nervous system.

John M. Maris, M.D., chief of Oncology at The Children’s Hospital of Philadelphia, co-authored the phase 3 clinical trial, which was led by Alice Yu, M.D., Ph.D., of the University of California, San Diego. Maris chairs the committee supervising the trial for the Children’s Oncology Group, a cooperative organization that pools resources from leading medical centers to study and devise new treatments for pediatric cancers.

Neuroblastoma, a cancer of the peripheral nervous system, usually appears as a solid tumor in the chest or abdomen. Neuroblastoma accounts for 7 percent of all childhood cancers, but due to its often aggressive nature, causes 15 percent of all childhood cancer deaths.

Yu will present the neuroblastoma study results on June 2 at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Fla. In advance of the meeting, ASCO published the findings online on May 14.

Maris explained that immunotherapy for cancer involves triggering the body’s immune system to attack cancer cells. Monoclonal antibodies are molecules customized to target particular cancers, while cytokines are naturally occurring signaling proteins that regulate the body’s immune responses.

In the current study, Children’s Oncology Group researchers studied 226 children with high-risk neuroblastoma. Half received the immunotherapy, while half received standard therapy (chemotherapy and stem cell transplantation). The patients who received the immunotherapy were 20 percent more likely than those in the standard therapy group to live disease-free two years after treatment. “This 20 percent improvement in preventing relapse led to a greater cure rate—the first substantial increase in cure rate for neuroblastoma for more than a decade,” said Maris.

The researchers halted the trial earlier than expected after early results showed the benefits of immunotherapy. “This experimental immunotherapy is poised to become part of the new standard of care for children with the aggressive form of neuroblastoma,” said Maris.

Maris added that the supply of the antibodies and cytokines used in the trial was limited, and that pediatric oncologists were seeking biotechnology companies to move the biological agents into commercial production to make the treatment readily available to children with neuroblastoma.

The Children’s Hospital of Philadelphia has one of the nation’s largest clinical and research programs in neuroblastoma. In 2008, Maris led a study that was the first to identify the gene location at which neuroblastoma originates. His laboratory continues to investigate how genes contribute to the disease, using that knowledge to devise new treatments.

Maris served as an oncologist for Alex Scott, the child with neuroblastoma who started a lemonade stand in 2000 to raise money for programs in childhood cancer. Now operated through the Scott family, the Alex’s Lemonade Stand Foundation supports ongoing research by members of the Children’s Oncology Group.

Source: American Society of Clinical Oncology, May 14, 2009

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  1. quiact says

    Over 100 years ago, a Russian histologist suggested stem cells be applied for scientific research. They are the human body’s equivalent of a generator, as they can renew, regenerate, and replicate under the right conditions.

    The apex of cellular therapy and regenerative/reparative medicine has been reborn after an 8 year moratorium that basically halted federal funding for stem cell research with most states in the U.S. Now the NIH can award grants to scientists involved with biomedical research involving stem cell therapy through the CMS to each state in the U.S.

    While never banned, stem cell research had limited funding during this time. And this was unfortunate, because there are several likely uses of stem cells.

    These uses include the replacement of tissues in the human body, as well as repairing cell types that are defective. Also, stem cells can deliver genetic therapies that are needed in certain patients.

    ESCs are totiplotent if obtained from the morula which is a pre-blastocyst stage. Normally, the stem cells are acquired from the blastocyst itself. From this source, the stem cells can be any cell in the human body except for the placenta, and are pluripotent.

    Embryonic stem cells are obtained from a 4 day old embryo called a blastocyst, and are pluripotent from this source. The blastocyst contains about 100 cells, and is not suitable at this stage for implantation into the uterine wall.

    The inner core of the blastocyst has about 20 cells, and this is where stem cells are obtained.

    These cells are unspecialized cells that can be developed or morphed into the over 200 cells available in the human body through differentiation, as ESCs are undifferentiated by nature.

    As such, they can become any human cell, as long as they are prevented from clumping or crowding together when explanted into cultures as they are propagated. After stem cells are cultured, they are moved to what are called stem lines.

    Until recently, ESCs were believed to be most beneficial instead of the adult stem cell alternative (ASC), as these stem cells are limited to application to the tissue the stem cells were obtained from only.

    However ASCs (somatic stem cells) now can be coerced into differentiation through plasticity (trans-differentiation). This likely will reduce if not eliminate those opposed to stem cell therapy because of moral and ethical reasons related to the utilization of ESCs.

    Thanks to molecular biology, four transcription factors control the transfer of genetic information from DNA to RNAS to regulate gene expression. So ASCs can have the same beneficial qualities as ESCs.

    In the past, viral vectors and exotic genes interfered with the purity of ASCs. Now ASCs are re-programmed using plasmids instead of viruses and oncogenes that can become detrimental for the patient treated.

    So now, ASCs can safely become induced pluripotent cells with the same potential as ESCs. As a result, the ASCs are free of genetic artifacts that potentially can interfere with transgene sequences.

    They are capable of, and are able to renew and reproduce with minimal effort, stem cells, under the right laboratory conditions.

    Human blood can be reproduced with stem cells under the right conditions, it has been shown by researchers.

    SCT can also be used to investigate disease states for better treatment options.

    Disease-specific stem cell lines, which are those cells that are pluripotent and are created with the same genetic errors of certain diseases, are studied for this reason.

    So there clearly is a huge potential for stem cell-based therapies. The first FDA approved clinical trial occurred early in 2009. This human trial will involve evaluating primarily the safety of ESCs designed to be used as treatment for spinal cord injury patients. The trial was submitted by Geron Corp.

    Pfizer, the largest drug company, has implemented stem cell research, as they are an asset to drug discovery by creating within the organization a regenerative medicine unit. Other large pharma companies are implemented similar research protocols for the same reasons.

    Geron Corp. in California is the world’s leading esc developer, and financed researchers at Univ. of Wisconsin, who isolated the first human esc in 1998.

    Stem cell therapy potentially can cure multiple sclerosis, among other diseases and those with damaged human tissue. The therapy prevents the advancement of disease, as well as reverses the neurological dysfunctions associated with MS. Patients are injected with their own stem cells obtained from their bone marrow, which are called haemopoietic stem cells.

    These particular stem cells are the origin of all blood cells. Further large clinical trials are needed to support these results. Studies have shown between 70 and 80 percent of MS patients who received stem cell therapy did not relapse afterwards.

    Allogenic, or donor transplants, have a risk of graft versus host disease. Autologous, which is the patient’s own stem cells, are preferable and most beneficial. Similar results from this autologous bone marrow transplant cellular therapy are seen with Chron’s disease as well.

    During the procedure, the immune system is reset so it is not in an autoimmune state where it attacks the human body. The process lasts about 2 months, and consists of 6phases:

    1. Initial chemo
    2. Release of stem cells
    3. Acquisition of stem cells
    4. Cells are then frozen until ready for transplant
    5. Second chemo to reduce leukocytes
    6. Autologous stem-cell transplant. Immune system is reset.

    Positive results from stem cell therapy are seen usually within a month, and patients can request another treatment about 6 months after the first treatment presently. This stem cell paradigm of therapy addresses the etiology of a disease state, instead of focusing on the symptoms only. As such, this is the practice of regenerative medicine with the implementation of SCT.

    Some believe ethical restraints are needed regarding the use of ESCs for therapeutic reasons. Yet they improve the quality of life of those with devastating diseases which involves suffering without any relief.

    So stem cell therapy and research may be the most right and ethical thing to do for such patients. Not only is the tremendous suffering relieved with those possessed with devastating diseases, their functional ability is restored for those who receive stem cell therapy.

    Embryos are acquired from fertility clinics (IVFs) that have thousands routinely stored and are abnormally fertilized. This means that they could never go on to become a human, and would be destroyed otherwise.

    Ironically, one could argue it is inappropriate to discard what may be valuable and ethical for others, potentially.

    Most couples with frozen embryos would gladly give them to such research, surveys have concluded.

    These embryos are believed by many to not be morally equivalent to human life, but only have the potential for life. And they are used for therapeutic cloning, known as somatic cell nuclear transfer, and not reproductive cloning.

    Ten states have banned this cloning out of ignorance, it seems. Bioethic principles, which are beneficience, or physician-centered decisions, as well as non-maleficence, which is first do no harm, are not corrupted.

    Furthermore, autonomy, which is the patient’s right to determine their health, and justice or fairness remain intact.

    Stem cells should be utilized for those terminally ill as well, many believe. Many are seeking stem cell therapy overseas due to depleting restrictions that exist in the U.S. presently. The United Kingdom is believed to be the leader in stem cell research presently.

    Dan Abshear

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