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A Review on the Antitumor Effect of
Extracellular Vesicle Encapsulated
Oncolytic Virus and Paclitaxel for
Lung Cancer Treatment
AMAL DHIVAHAR S (UR16BT060)
DEPARTMENT OF BIOTECHNOLOGY,
KARUNYA INSTITUTE OF TECHNOLOGY & SCIENCES, COIMBATORE – 641114, TAMIL NADU, INDIA.
Abstract
 The common combination of surgery with radiotherapy or chemoradiotherapy seems to remain inefficient in
some advanced cancer patients with its complications and side effects. Oncolytic viruses are known for their anti-
cancer mechanisms enabling the possibility for improved efficiency in cancer therapy. Chemotherapeutics combined
with oncolytic viruses exhibit stronger cytotoxic responses and oncolysis. According to the authors, investigating the
systemic delivery of the oncolytic adenovirus and paclitaxel encapsulated in extracellular vesicles (EV)
formulation in vitro has shown a significant increase in the transduction ratio and the infectious titer when compared
with them used alone. The ability of this EV formulation to reduce the in vivo tumor growth in animal xenograft
model of human lung cancer has been demonstrated through this research work and it has proved to be an enhanced
effect indeed. The presentation will be a review of this work, which claims to provide a promising approach
combining anticancer drugs and viral therapies by intravenous EV delivery, which serves as a strategy for lung
cancer treatment.
 Keywords: Extracellular vesicles, Oncolytic viruses, Oncolysis, Chemotherapeutics, Paclitaxel, Xenograft animal
Xenograft animal model, Lung cancer treatment
Lung Cancer
Prevailing cause of cancer-related morality with NSCLC
85%
Accounting for most lethal cancers
worldwide in both the genders
>30%
A549 – Human Adenocarcinomic Alveolar Basal Epithelial
Cells (Fan et al., 2006).
1972
Oncolytic Virotherapy
viruses - specifically
engineered - infect,
replicate in and
kill cancer cells
instead of normal
cells where their
normal functions
are restricted
Virus replication in
tumor cells
eventually leads to
cell lysis
allowing the new
virus progeny to
spread to
surrounding cells
and even
to distant
metastases
through circulation
Extracellular Vesicles (EVs)
 naturally occurring cargo delivery agents with the potential to be used as drug delivery
vehicles since they can transfer biological molecules even over long distances within the
body.
 The lipid membrane of EVs can protect the cargo from degradation by body fluids and
further improved uptake by the target cells
Paclitaxel
 Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy
medication used to treat a number of types of cancer.
 This includes ovarian cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer,
and pancreatic cancer.
 It is given by injection into a vein (intravenous).
 Cell culture: 2.6×10`6 A549 Human Lung cancer cell line
 Oncolytic virus: Ad5D24-CpG
 Paclitaxel : dissolving PTX into di-methyl sulfoxide (DMSO) – 50mM stock
 EVs: 2.6×106 A549 cells were plated into T-175 flask in medium supplemented with 5%
FBS – differential centrifugation - ultracentrifugation
 Production of EV-Virus and EV-Virus-PTX formulations: 2.6×106 of A549 cells were
infected with 10 viral particles/cell of Ad5D24CpG
 Quantification of PTX present in EV-Virus-PTX, Size distribution analysis by
nanoparticle tracking analysis (NTA), Zeta potential analysis by electrophoretic light
scattering, HIM microscopy, etc
Methods (Garofalo et al., 2018)
Transduction Assay
Cells were seeded at a density of 1×104 cells/well in 96-well plates - treated in triplicates
with an oncolytic adenovirus (Ad5D24Rfp encoding for the red fluorescent protein
(10vp/cell)):
 control EVs (10 particles/cell)
 EV-Virus (10 particles/cell),
 EV-PTX (10 particles/cell,5 μM of PTX),
 EV-Virus-PTX (10 particles/cell, 5 μM of PTX) or
 Virus and PTX separately (Virus+PTX) (10 vp/cell, 5 μM of PTX).
Nano tracking
analysis (NTA).
Helium Ion Microscopy (HIM)
ZetaSizer Nano Malvern
In vivo study results
iv dose & Survival rate
A Background lesion
Mild lymphocyte hyperplasia
Mild lymphocyte hyperplasia &
hyperplasia
Mild hyperplasia
necrotic remnants of cells
No necrosis
large number of
neutrophils
large cavity with intraluminal
blood and proteinaceous fluid.
Graphical Abstract
GRAPHICAL
ABSTRACT
Conclusion
“the systemic delivery of both
oncolytic virus and paclitaxel
encapsulated in EVs resulted in
improved drug efficacy and reduced
off-target toxicity”
Thank you.

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A Review on the Antitumor Effect of Extracellular Vesicle Encapsulated Oncolytic Virus and Paclitaxel for Lung Cancer Treatment

  • 1. A Review on the Antitumor Effect of Extracellular Vesicle Encapsulated Oncolytic Virus and Paclitaxel for Lung Cancer Treatment AMAL DHIVAHAR S (UR16BT060) DEPARTMENT OF BIOTECHNOLOGY, KARUNYA INSTITUTE OF TECHNOLOGY & SCIENCES, COIMBATORE – 641114, TAMIL NADU, INDIA.
  • 2. Abstract  The common combination of surgery with radiotherapy or chemoradiotherapy seems to remain inefficient in some advanced cancer patients with its complications and side effects. Oncolytic viruses are known for their anti- cancer mechanisms enabling the possibility for improved efficiency in cancer therapy. Chemotherapeutics combined with oncolytic viruses exhibit stronger cytotoxic responses and oncolysis. According to the authors, investigating the systemic delivery of the oncolytic adenovirus and paclitaxel encapsulated in extracellular vesicles (EV) formulation in vitro has shown a significant increase in the transduction ratio and the infectious titer when compared with them used alone. The ability of this EV formulation to reduce the in vivo tumor growth in animal xenograft model of human lung cancer has been demonstrated through this research work and it has proved to be an enhanced effect indeed. The presentation will be a review of this work, which claims to provide a promising approach combining anticancer drugs and viral therapies by intravenous EV delivery, which serves as a strategy for lung cancer treatment.  Keywords: Extracellular vesicles, Oncolytic viruses, Oncolysis, Chemotherapeutics, Paclitaxel, Xenograft animal Xenograft animal model, Lung cancer treatment
  • 3. Lung Cancer Prevailing cause of cancer-related morality with NSCLC 85% Accounting for most lethal cancers worldwide in both the genders >30% A549 – Human Adenocarcinomic Alveolar Basal Epithelial Cells (Fan et al., 2006). 1972
  • 4. Oncolytic Virotherapy viruses - specifically engineered - infect, replicate in and kill cancer cells instead of normal cells where their normal functions are restricted Virus replication in tumor cells eventually leads to cell lysis allowing the new virus progeny to spread to surrounding cells and even to distant metastases through circulation
  • 5. Extracellular Vesicles (EVs)  naturally occurring cargo delivery agents with the potential to be used as drug delivery vehicles since they can transfer biological molecules even over long distances within the body.  The lipid membrane of EVs can protect the cargo from degradation by body fluids and further improved uptake by the target cells
  • 6. Paclitaxel  Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer.  This includes ovarian cancer, breast cancer, lung cancer, Kaposi sarcoma, cervical cancer, and pancreatic cancer.  It is given by injection into a vein (intravenous).
  • 7.  Cell culture: 2.6×10`6 A549 Human Lung cancer cell line  Oncolytic virus: Ad5D24-CpG  Paclitaxel : dissolving PTX into di-methyl sulfoxide (DMSO) – 50mM stock  EVs: 2.6×106 A549 cells were plated into T-175 flask in medium supplemented with 5% FBS – differential centrifugation - ultracentrifugation  Production of EV-Virus and EV-Virus-PTX formulations: 2.6×106 of A549 cells were infected with 10 viral particles/cell of Ad5D24CpG  Quantification of PTX present in EV-Virus-PTX, Size distribution analysis by nanoparticle tracking analysis (NTA), Zeta potential analysis by electrophoretic light scattering, HIM microscopy, etc Methods (Garofalo et al., 2018)
  • 8. Transduction Assay Cells were seeded at a density of 1×104 cells/well in 96-well plates - treated in triplicates with an oncolytic adenovirus (Ad5D24Rfp encoding for the red fluorescent protein (10vp/cell)):  control EVs (10 particles/cell)  EV-Virus (10 particles/cell),  EV-PTX (10 particles/cell,5 μM of PTX),  EV-Virus-PTX (10 particles/cell, 5 μM of PTX) or  Virus and PTX separately (Virus+PTX) (10 vp/cell, 5 μM of PTX).
  • 9. Nano tracking analysis (NTA). Helium Ion Microscopy (HIM) ZetaSizer Nano Malvern
  • 10. In vivo study results
  • 11. iv dose & Survival rate
  • 12. A Background lesion Mild lymphocyte hyperplasia Mild lymphocyte hyperplasia & hyperplasia Mild hyperplasia necrotic remnants of cells No necrosis large number of neutrophils large cavity with intraluminal blood and proteinaceous fluid.
  • 14. Conclusion “the systemic delivery of both oncolytic virus and paclitaxel encapsulated in EVs resulted in improved drug efficacy and reduced off-target toxicity”