26 / 26
Page 64
Volume 3
August 5-6, 2019 | Singapore
CANCER RESEARCH AND PHARMACOLOGY
STRUCTURAL BIOCHEMISTRY, STEM CELLS AND MOLECULAR BIOLOGY
24
th
International Conference on
International Congress on
&
Cancer Research 2019 & Structural Biochemistry 2019
August 5-6, 2019
Journal of Cancer and Metastasis Research
Receptor binding of a novel bifunctional TGF-β1/PD-L1 fusion protein elicited a down-
regulated immune signature
Marvin I De los Santos
University of the Philippines Diliman, Philippines
Statement of the Problem
: There are more than 80 clinical distinct types of autoimmune diseases (AID) and their collective
global prevalence rate have increased to >10%. Until now, treatment regimen has relied heavily on the use of drugs (i.e. NSAIDs,
glucocorticoids and DMARDs) that down-regulate
the entire body’s immune response. High-dose and
long-term medication with these drugs have been
found to correlate with susceptibility to infections
and tumorigenesis. Preclinical studies targeting the
receptors of transforming growth factor superfamily
such as TGF-β1 has implicated possible use of
this molecule in AID management and treatment.
However, researchers have reported several
drawbacks of targeting TGF-β1 signaling, as they
found its involvement in prevention but not reversal
of AID. Another group of immune checkpoint
protein, the PD-1/PD-L1 axis, has been found to
down-regulate immune response and have clinical
implications for treatment of the disease. This
study aims to utilize the combinatorial immune-
downregulating activities of TGF-β1 and PD-L1 by
generating a fusion product which has never been
described before.
Methodology
: We were able to previously successfully clone and generate a fusion gene construct of TGF-β1 and PD-L, validated
by DNA sequencing. The study focused next on characterizing the bifunctional binding of the proteins with their respective
receptors by co-immunoprecipitation (co-IP) and reverse co-IP experiments coupled with pathway analysis by qRT-PCR.
Findings and Results
: A 70 kDa TGF-β1/PD-L1 fusion protein was demonstrated to bind TGF-β1 receptors such as TGF-β
receptor 1 and PD-L1 target receptor, PD-1, in co-IP and reverse co-IP experiments. Gene expression analysis showed that these
interactions are functional and elicit gene expression signature that is seen in suppressed immunity using a cell line model.
Conclusion and Significance
: TGF-β1/PD-L1 fusion protein may represent a new class of immunotherapy for treatment and
management of autoimmune diseases in the future.
midelossantos1215@gmail.com