PHCbi-Panasonic eBook - 17

Cell Therapy Today * New Developments in Immunotherapy * Immuno-Oncology Enhances Battlespace Awareness

Preconditioning treatments may be added in
future trials. "We're very cautious about how to
proceed," Dr. Gilham admits. "But we're encouraged by what we've seen to date."

Determining Whether Patients
Will Benefit
Immunotherapy has revolutionized how doctors
treat the disease. However, not all patients
respond to the new therapies. Each individual's
immune system is wired slightly differently.
Consequently, some people are more sensitive to
cancer while others are less so. Recognizing these
differences in sensitivity, researchers are now
looking for biomarkers that can predict which
patients will respond to treatment.
The first biomarker assays approved by the FDA
targeted PD-L1 expression, but because tumor
biology and immunity are complex, a single type
of biomarker is not sufficient. That has led investigators to conduct biomarker investigations
spanning protein expression, genomics, and transcriptomics. For example, researchers are looking
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at the correlation between genomic markers and
PD-L1 expression.
Maher Albitar, M.D., senior vice president, chief
medical officer, and director of research and
development at NeoGenomics Laboratories, is
leading a study of genes implicated in non-small
cell lung cancer (NSCLC) and colorectal cancer.
Dr. Albitar's group is evaluating whether these
genes, which include FGFR1, FGFR2, FGFR3, SRC,
JAK3, ERBB4, ERBB2, TP53, and SMAD4, correlate
with PD-L1 expression.
The investigators found that PD-L1 expression is
significantly lower in colorectal cancer compared
with NSCLC. They also determined that in NSCLC
patients, PD-L1 expression is significantly higher
in tumors with mutated TP53. So, there's a correlation between TP53 mutation in NSCLC and the
expression of PD-L1, but not in colorectal cancer,
even though the tumor types had similar rates of
TP53 mutation.
"This suggests a possible difference in the mechanism of regulating PD-L1 expression between

the two tumor types," the team wrote in a poster4
available on the company's website. Negative
correlations between PD-L1 expression and EGFR
in lung cancer and BRAF in melanoma have also
been identified, along with positive correlations
between PD-L1 expression and Met amplification
in lung cancer and between PD-L1 expression
and the lack of TP53/Ras mutations in colorectal
cancer, Dr. Albitar notes in a related webinar.5

Biomarkers Through Imaging
Molecular imaging is a noninvasive way to evaluate tumors and, as a result, could help clinicians
accurately select patients for immuno-oncology
treatments or monitor their responses. Current
imaging technology falls short of this promise,
though. It does not allow doctors to evaluate
trafficking of activated T cells into tumors or how
treatment affects the tumor.
At Imaging Endpoints, Ronald L. Korn, M.D.,
Ph.D., the company's founder, chairman, and
chief medical officer, has been working with
colleagues to integrate positron emission

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