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Immunoscore Could Be 'Transformational' in Oncology
Zosia Chustecka, news editor for Medscape Oncology
September 24, 2012 (Beijing, China) — A new approach to prognostication, developed initially for use in
colorectal cancer, homes in on the body's immune response to the tumor instead of focusing on the tumor
itself.
The immunoscore approach measures cytotoxic T lymphocytes that infiltrate the tumor; the more there are, the
stronger the immune response against the tumor. This approach has been shown to better correlate with
patient prognosis. In addition, some research suggests that it could be predictive and identify patients who
need further treatment.
Currently, most tests used for prognostication and prediction home in on the tumor itself. Commercially
available tests, such as the Oncotype DX test, use a core sample of the tumor to analyze gene mutations or
gene signatures.
The immunoscore approach looks for tumor infiltrating cells not only in a core sample, but also in a sample
taken at the tumor margins. This is where the immune system launches its attack on the tumor, Bernard Fox,
PhD, immediate past president of the Society for Immunotherapy of Cancer (SITC), explained.
Dr. Fox highlighted the immunoscore approach in his keynote speech reviewing immunotherapy for cancer
here at the Chinese Society of Clinical Oncology (CSCO) 15th Annual Meeting, during a session on
immunotherapy organized jointly by CSCO, SITC, and the Chinese American Hematologist Oncologist Network
(CAHON).
He is enthusiastic about immunoscore. "I think it has the potential to be transformational for the field of
oncology," he told Medscape Medical News.
A number of small clinical trials of the immunoscore approach have already been published, and now a large
validation study is underway, he said.
The SITC-led immunoscore validation project is supported by World Immunotherapy Council. It was formed as
a result of a manuscript entitled Defining the Critical Hurdles in Cancer Immunotherapy, which was produced at
a SITC-organized Cancer Immunotherapy Summit. Dr. Fox noted that the current CSCO president, Shu-Kui
Qin, MD, has supported CSCO participation in such meetings.
Dr. Qin, senior vice-president of the Jiangsu Nanjing Jingdu Hospital in Nanjing, and director of clinical trials in
China, told Medscape Medical News that currently "in clinical practice, we use the TNM classification for
cancer, but we should pay attention to immune function, because it influences clinical outcomes significantly."
"SITC has proposed that we use immunoscore to do this, and CSCO totally agrees with this approach," he
said. "But this is a new system; it needs to be validated and then incorporated into clinical practice so that we
can improve clinical practice and the efficiency and safety of our treatments."
The Immunoscore Validation Study involves a retrospective analysis of tumor samples from 6000 patients. It is
being conducted at 22 centers across the world, including Australia, Canada, China, Europe, India, Japan, and
the United States; results are expected at the end of this year.
Measuring Cancer Killer Cells
The immunoscore developed for colorectal cancer measures 2 markers of tumor infiltrating T lymphocytes:
CD3 and CD8.
Tumor tissue samples are stained to identify patients who are positive for CD3 and CD8. In addition, a
standardized software application is used to determine the number of cancer killer cells in the sample, which
objectively quantifies immune response. "This is really important because it means that pathologists around the
world will get the same standardized results," Dr. Fox said.
In patients identified as being positive for CD3 and CD8, an immune response has been mounted against the
tumor. Clinical trials have established that these patients have a better prognosis than patients who test
negative for these markers, Dr. Fox explained. It is assumed that the immune response that the body has
mounted against the tumor is keeping it in check.
Clinical trial data show that many more patients with stage I or II than with stage III colon cancer are positive for
CD3/CD8. We know that these earlier-stage patients have a much better prognosis than those with stage III
disease, Dr. Fox noted.
In fact, the prognosis is so good that the treatment for stage I and II colon cancer is usually surgery alone. Dr.
Fox said that the immunoscore approach can be used to identify patients who have a low immune response,
and hence a worse prognosis, who would benefit from adjuvant therapy. These patients could then be enrolled
in a clinical trial, he added.
A recent study (J Clin Oncol. 2011;29:610-618), which summarized several years of work, reported that CD8+
T cells were a better indicator of risk for recurrence than standard tumor staging in 559 patients with colorectal
cancer.
In an editorial accompanying that study (J Clin Oncol. 2011:29:601-603), Elizabeth K. Broussard, MD, and
Mary L. Disis, MD, from the Center for Translational Medicine in Women's Health at the University of
Washington in Seattle, write that the study lays the foundation for the immunoscore approach "as a clinical
prognostic marker at any stage of colorectal cancer."
Another clinical trial used this approach in patients with colorectal cancer that had metastasized to the liver,
and showed a strong association between the local immune cell profile and chemotherapy outcome (Cancer
Res. 2011;71:5670-5677). "This clearly extends the observed role for the immune system in primary [colorectal
cancer] into metastatic lesions and further into chemotherapy efficacy," those authors write.
Although most of the immunoscore work so far has been carried out in patients with colon cancer, some work
suggests that it can be used in other types of cancer, perhaps using other markers, Dr. Fox noted.
Immunotherapy to Boost Response
In the future, there is hope that immunotherapy will boost immune response to tumors in patients who score
low on the test.
Dr. Fox has a vested interest in this approach; he is a cofounder and chief executive officer of UbiVac, a
company working to develop such an immunotherapy. The company is about to begin a phase 2 trial in NSCLC
patients, and a phase 2 trial is planned for breast cancer patients. The product is a vaccine, delivered every 3
weeks for 7 cycles, that contains particles of the tumor presented in such a way that they overcome the body's
tolerance and it mounts an immune response, Dr. Fox explained. The tumor particles contained in the vaccine
are known as DRibbles. They are formed by outpockets on the tumor cell membrane, known as blebs, and
contain defective ribosomal products, known as DRiPs. It is these DRiPs in the blebs that are known as
DRibbles, Dr. Fox explained.
This is a novel approach to cancer vaccine development. There are data to suggest that the same product
could work in many different cancer types, Dr. Fox noted. Current cancer vaccines are typically specific to a
single cancer type; for example, sipuleucel-T (Provenge, Dendreon) is specifically for prostate cancer.
There has been keen interest from China in immunotherapy as an approach to cancer treatment, Dr. Fox said.
There is great interest in cellular therapy, which is already being used to treat cancer patients, but currently
there is no formal regulation of this. This has caused some concern within the medical oncology leadership; at
the CSCO meeting, there was a session dedicated to the regulation of cellular therapy. Liu Ke MD, PhD, past
president of CAHON, outlined the regulations in place in the United States, and Rik Scheper, PhD, from the
Free University of Amsterdam, the Netherlands, outlined those in Europe. Both the United States and Europe
put new regulations in place after the highly publicized death in 1999 of a patient participating in a gene therapy
trial.
In an overview of immunotherapy in the treatment of lung cancer, Yilong Wu, MD, vice-president of the
Guangdong General Hospital and president of the Guangdong Cancer Institute in China, said that many
different approaches have been tested but, to date, none has been successful. Immunotherapy is undergoing a
renaissance though; recently several phase 2 studies have yielded results promising enough to move to
phase 3, he explained. However, for the time being, immunotherapy must be considered experimental, he
noted.
According to Dr. Wu, many questions remain about how to measure responses: When should an immune
response be assessed? How should it be measured? When should immunotherapy should be used? The best
chance of it working is early on in cancer, while it is still establishing itself; however, new immunotherapeutics,
like all new products for cancer, are initially tested in patients with late-stage cancer, when the disease is
metastatic. At that stage, "are we sending in a boy to do a man's work?" Dr. Wu wondered.
Dr. Fox reports receiving funding from Bristol-Myers Squibb for some research studies with Immunscore; and
serving as a consultant for Micromet (Amgen), Bristol-Myers Squibb, MannKind, BioSante, and Biovax.
Chinese Society of Clinical Oncology (CSCO) 15th Annual Meeting. Presented September 20, 2012.
Medscape Medical News © 2012 WebMD, LLC
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