Immunotherapy in High-Risk Pediatric Sarcomas including Ewing's Sarcoma Shows Promising Response

http://www.aacr.org/home/public–media/news.aspx?d=1112

http://clincancerres.aacrjournals.org/cgi/content/abstract/14/15/4850

Requests for reprints: Crystal L. Mackall,
Pediatric Oncology Branch, Center for Cancer Research, National Cancer
Institute, NIH, 10-CRC/1W-3940, 10 Center Drive, MSC 1104, Bethesda, MD
20892-1104. Phone: 301-402-5940; Fax: 301-451-7052; E-mail
Crystal L. Mackall: cm35c@nih.gov

Immunotherapy in High-Risk Pediatric Sarcomas including

Ewing's Sarcoma Shows Promising Response

August 1, 2008

PHILADELPHIA – Based on a pilot study in children with sarcoma,
researchers at the National Institutes of Health (NIH) believe that
immunotherapy could prove beneficial in treating high-risk forms of
this cancer.

The researchers tested a novel dendritic vaccine as well as a
standard flu vaccine to potentially strengthen the immune system post
chemotherapy. Their findings, published in the August 1 issue of Clinical Cancer Research,
a journal of the American Association for Cancer Research, show that
although the dendritic vaccine they tested did not perform as well as
hoped, children participating in the study responded well to the
standard flu vaccine- suggesting that a strategy to bolster immune
function in these patients holds promise for fighting their cancer.

Researchers also found that survival in these patients was at the
higher end of what is generally seen with recurrent and/or metastatic
Ewing's sarcoma (ESFT) or alveolar rhabdomyosarcoma (AR) – the two
sarcomas tested in this single arm study.
  The 22 enrolled patients who
did not receive immunotherapy had a 31 percent five-year overall
survival, compared to 43 percent five-year survival in 30 patients who
ultimately received the novel immunotherapy.

Although the study is small, these early findings are promising,
says the study's senior investigator, Crystal Mackall, M.D., of the
National Cancer Institute's (NCI) Pediatric Oncology Branch. “We need
new therapies. While outcomes overall for these tumors have improved
during the past 40 years, there has not been substantial improvement
for patients with metastatic or recurrent disease. This study shows
that immunotherapy is safe and well tolerated, and could ultimately be
beneficial for this high risk population. Mackall calls the study a
rational approach to improving treatment of ESFT and AR. “We now know
that the immune system of patients recovering from chemotherapy is
malleable, so we just need to find the best immunologic approach to
exploit this window of opportunity,” she said.

Both ESFT and AR develop due to chromosomal translocations, which
fuse a gene from one chromosome to a different chromosome. The
dendritic vaccine included peptides derived from each patient's
individual cancer in a way that was designed to alert a patient's
immune system to the unique genetic alteration on the cancer cells.
In this clinical trial of 52 patients, researchers attempted to use
immunotherapy as “consolidation” therapy – that is, after standard
therapy provided a remission. Patients underwent aphaeresis to harvest
blood lymphocytes that were then frozen. From this, dendritic cells
were later extracted. These are cells that present an antigen to T
cells and other immune system fighters in order to elicit a response.

All patients then had chemotherapy, radiation or surgery, as
appropriate, and in some cases a stem cell transplant to induce
remission. The 30 patients who initiated immunotherapy received a
common flu vaccine, as well as their own lymphocytes and their own
dendritic cells, which had been infused with tumor antigens. Some of
these patients also received interleukin-2, which stimulates activity
of T cell lymphocytes.

“The good news was the surprisingly nice T cell response patients
had to the flu vaccination, even relatively soon after completing
chemotherapy,” Mackall said. “That shows that the general idea of using
immunotherapy following chemotherapy to prevent recurrence is not a
flawed one. Chemotherapy depleted the immune system, but we could
restore it.”

The bad news, she added, is that the dendritic vaccine “was not very
immunogenic. We have a long way to go to optimizing this vaccine.”
Current studies are underway to test a new version of the vaccine,
which utilizes more mature dendritic cells and tumor lysate in lieu of
the translocation peptides. Ultimately, effective immunotherapy
requires that one is capable of reproducing a strong and sustained
immune response to tumor antigens,” she said.

Mackall also notes that the vaccine in this trial was tested in
patients whose cancer had recurred or metastasized. If the favorable
safety profile continues and the efficacy of the vaccine is improved
with the subsequent versions, one could ultimately consider the use of
immunotherapy to consolidate remission in lower risk populations.


# # #

The mission of the American Association for Cancer Research is to
prevent and cure cancer. Founded in 1907, AACR is the world's oldest
and largest professional organization dedicated to advancing cancer
research. The membership includes more than 28,000 basic, translational
and clinical researchers; health care professionals; and cancer
survivors and advocates in the United States and 80 other countries.
AACR marshals the full spectrum of expertise from the cancer community
to accelerate progress in the prevention, diagnosis and treatment of
cancer through high-quality scientific and educational programs. It
funds innovative, meritorious research grants. The AACR Annual Meeting
attracts more than 17,000 participants who share the latest discoveries
and developments in the field. Special conferences throughout the year
present novel data across a wide variety of topics in cancer research,
treatment and patient care. AACR publishes five major peer-reviewed
journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists. CR
provides a forum for sharing essential, evidence-based information and
perspectives on progress in cancer research, survivorship and advocacy.

Media Contact:
Jeremy Moore
267-646-0557
Jeremy.moore@aacr.org

Leave a Reply

Your email address will not be published. Required fields are marked *