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LIFESCIENCELEADER.COM JANUARY 2015
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addition, combinations of immune check-
point inhibitors with other mechanisms
such as cancer vaccines, cell therapies,
and immune-activating antibodies are
now being tested in the clinic and will
likely be part of the oncologist's armamen-
tarium in the future.
Backbone therapy?
It is probably too early to tell whether one
axis will be the backbone of all immu-
no-oncology combinations. There will
be variability from tumor type to tumor
type and even among patients. Already,
data suggest that the CTLA-4 and PD-1/
PD-L1 pathways are more relevant for
drug therapy in some tumors than oth-
ers. Our understanding of therapeutic
selection will become more refined as the
roles of particular immune checkpoints
are better elucidated across a wide range
of tumors. Five Prime is developing novel
checkpoints that could be used in combi-
nation with the clinically validated path-
way inhibitors, but may also be used as a
single agent in tumors that do not respond
well to those therapies.
Combo criteria?
Selection of specific immuno-oncology
combinations will likely be done by char-
acterizing immune checkpoint proteins
(or the nucleic acid transcripts that code
for such proteins) present in a patient's
tumor or immune cells. In addition, the
safety profile of each drug should be con-
sidered before combining them.
Narrow or wide applications?
Five Prime focuses on more generalizable
immuno-oncology approaches that can
be given to all patients who are likely to
have the relevant target for a drug such
as a monoclonal antibody. However, this
doesn't mean that we can ignore what
the patient's tumor looks like. As patients,
physicians, and payers demand better out-
comes and probabilities of success, there
will be demand for biomarker molecular
profiling to select immunotherapies most
likely to result in durable responses and
improved survival.
Personal or broad?
Patient cell-based approaches, such as
artificial T cells expressing tumor-recog-
nizing receptors (also known as chimeric
antigen receptor-T cells, or CAR-T cells),
are intriguing, and some of the Phase 1
data, particularly in hematologic malig-
nancies, have been exciting. The CAR-T
cells are reintroduced into the patient
and hopefully recognize and kill the can-
cer cells. So every patient represents
essentially a separate manufacturing lot.
Despite encouraging data, significant