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J Med Oncl Ther 2017 | Volume 2 Issue 4
Oncology and Biomarkers Summit
November 27-28, 2017 | Atlanta, USA
Annual Congress on
S
mall cell lung cancer (SCLC) patients can develop
autoimmune responses against neuronal proteins
misexpressed in their tumors. Rarely, this response is severe,
resulting in debilitating disease and death. One family of
antigens is the neuronal embryonic lethal altered visual
system-like (ELAVL) RNA-binding proteins (“Hu” proteins).
All SCLC tumors misexpress neuronal ELAVL proteins, most
commonly ELAVL4. Although less than 1% of SCLC patients
develop high titer anti-ELAVL antibodies and exhibit
paraneoplastic
encephalomyelitis/sensory
neuropathy
(PEM/SN), lower titer antibodies are seen in about 15-20%
of SCLC patients without autoimmune symptoms. Based
on the sequence and presumably unstructured nature
of the N-terminal region of neuronal ELAVL proteins, we
hypothesized that in the context of SCLC these proteins can
undergo isoaspartylation, an immunogenic post-translational
modification, triggering an immune response in a subset of
SCLC patients. Indeed, we recently showed that neuronal
ELAVL proteins undergo isoaspartylation
in vitro
and
in
vivo
, that this makes these proteins highly immunogenic
and that sera from SCLC patients react specifically with
the isoaspartyl-prone N-terminal region of ELAVL4. Here,
we build upon these results by using a SCLC mouse model
to develop and test a variety of immunization methods to
determine whether mice can be protected from induced
SCLC, laying the foundation for immunotherapy.
e:
ilaird@usc.eduDevelopment of SCLC immunotherapy using isoaspartylated ELAVL4
Laird-Offringa
Keck School of Medicine of USC, USA