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J Med Oncl Ther 2017 | Volume 2 Issue 4
allied
academies
Oncology and Biomarkers Summit
November 27-28, 2017 | Atlanta, USA
Annual Congress on
D
uring tumorigenesis, human cells were induced to express
a family of MHC I-chain related molecules A and B (MICA
and MICB, generally termed MIC) on the surface which serve
as the ligands for the activating immune receptor NKG2D
expressed by all human NK, CD8 T, NKT and subsets of
γ
δ
T cells. Theoretically, engagement of NKG2D by tumor cell
surface MIC deemed to signal and provoke the immune system
to eliminate transformed cells. Clinically, almost all advanced
tumors in cancer patients produce soluble MIC through
proteolytic shedding mediated by metalloproteases, or by
release in exosomes derived from the cell membrane. Tumor-
derived sMIC is known to be highly immune suppressive and
profoundly insults the immune system by downregulating
receptor NKG2D expression on effector NK and T cells, driving
the expansion of tumor-favoring myeloid suppression cells,
skewing macrophages into alternatively activated phenotypes
and perturbing NK cell peripheral maintenance. High levels of
serum sMIC significantly correlate with advanced diseases of
many types of cancer. These observations clearly endorse sMIC
tobe a cancer immune therapeutic target. However, due tomice
lack homologues to human MIC, this concept was not proven
until our recent studies. Using a “humanized” MIC-transgenic
spontaneous mouse model which recapitulates the NKG2D-
mediated onco-immune dynamics of human cancer patients,
we show that neutralizing circulating sMIC with a first-in-field
monoclonal antibody B10G5 alleviates the immune suppressive
effect of sMIC and revamps endogenous anti-tumor immune
responses. Therapy with B10G5 results in effective debulking of
primary tumor and elimination of metastasis, with no observed
toxicity. Furthermore, we show that clearing sMIC with B10G5
also enhanced the efficacy of other cancer immunotherapeutic
modalities, such as immune checkpoint blockade or adoptive
cell-based therapy pre-clinically. Our study has launched a
new avenue of cancer immunotherapy which can be readily
translated into clinical trials.
Speaker Biography
Jennifer Wu joined Northwestern University in August 2017 as a tenured Professor
in Urology. Dr. Wu previously served as a Professor of Microbiology and Immunology
at the Medical University of South Carolina and the University of Washington. Dr.
Wu obtained her PhD from the University of British Columbia in Canada followed
by post-doctoral training in Fred Hutchinson Cancer Research Center (FHCRC) and
faculty position at the University of Washington. Dr. Jennifer Wu’s research focuses
on understanding how cancer cells edit the immune system with the ultimate goal to
develop effective immune therapy to control cancers.
e:
jennifer.wu@northwestern.eduJennifer Wu
Northwestern University, USA
Novel antibody for cancer immunotherapy: Beyond and synergistic with immune
checkpoint blockade therapy