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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
Circulating tissue specific exosome profiles for noninvasive monitoring of immunologic rejection in
transplantation
Prashanth Vallabhajosyula
University of Pennsylvania, USA
Statement of the Problem: Organ/tissue transplantation
remains the only life-saving, curative therapy in patients
with end stage diseases of the heart, liver, kidney, and
lungs. Transplant patients are placed on obligatory
immunosuppressive medications to prevent organ rejection,
thus placing them at higher risk for malignancies and
infectious complications. Rejection and immunosuppression-
related complications remain the primary causes of
morbidity and mortality in transplant patients. Yet to this
date, there is a critical need for development of biomarkers
for noninvasively monitoring rejection. We proposed that
circulating exosomes, microvesicles carrying tissue-specific
nucleic acids and proteins, reflect condition specific changes
imposed on the transplanted tissue. If so, transplant
tissue specific exosome profiling would constitute a novel
biomarker platform for monitoring transplant rejection. We
studied this concept in animal models of islet, heart, and
lung transplantation, and further validated its translational
potential in clinical setting.
Findings: In animal models of islet and heart transplantation,
we demonstrated that circulating transplant tissue specific
exosome quantitative and cargo profiles are significantly
decreased early in the acute rejection process. This change
was noted to occur in a time sensitive manner, before
histological evidence of rejection/ injury to the transplanted
tissue. Further, in clinical islet transplantation, transplant
islet specific exosomes were reliably tracked in 4 patients
over long term follow-up of over 5 years, suggesting
that transplant exosomes can be utilized for noninvasive
surveillance in the clinical setting. In addition, in heart
transplant patients (n=5), we demonstrated that circulating
donor heart specific exosomes can be reliably tracked in the
perioperative setting.
Conclusions & Significance: Circulating transplant tissue
specific exosomes accurately herald early acute rejection
in animal models of transplantation. These potential
noninvasive biomarkers can also be reliably tracked in
the clinical setting. Further investigations may reveal the
noninvasive diagnostic potential of transplant tissue specific
exosome platform.
Speaker Biography
Prashanth Vallabhajosyula received his Bachelor of Science and Masters of Science
in molecular biophysics and biochemistry, along with his Doctor of Medicine degrees
from Yale University, New Haven, CT. He completed his residency in general surgery at
Johns Hopkins Hospital, Baltimore, MD. During this period, he did a clinical fellowship
in upper gastrointestinal surgery at Oxford-Radcliffe Hospitals, Oxford, United
Kingdom. He attended the Hospital of University of Pennsylvania for a fellowship in
cardiothoracic surgery, and completed a sub-specialization year in aortic surgery, along
with endovascular and minimally invasive techniques. His surgical interests are in
aortic surgery, endovascular surgery and thoracic organ transplantation.
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