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April 15-16, 2019 | Milan, Italy

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Joint Event on

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EPIDEMIOLOGY AND NUTRITION

World Congress on

CELL AND GENE THERAPY

International Conference on

Cell and Gene Therapy 2019 & Public Health Congress 2019

Archives of General Internal Medicine | ISSN: 2591-7951 | Volume 3

THE IMPACT OF Γ-IRRADIATION ON THE INDUCTION OF BYSTANDER KILLING BY

GENETICALLY ENGINEERED OVARIAN TUMOR CELLS: IMPLICATIONS FOR CLINICAL

USE AS CANCER VACCINES

Jehad Zweiri

University of Liverpool, United Kingdom

ellular based therapeutic approaches for cancer rely on careful consideration of finding the optimal cell to

execute the cellular goal of cancer treatment. Cell lines and primary cell cultures have been used in some

studies to compare the

in vitro

and

in vivo

efficacy of autologous vs allogeneic tumour cell vaccines. This study

examines the effect of γ-irradiation on a range of tumor cell lines in conjunction with suicide gene therapy of

cancer. To determine the efficacy of this modality, a series of

in vitro

and

in vivo

experiments were conducted

using genetically modified and unmodified tumor cell lines. Following co-culture of HSV-TK modified tumor

cells and unmodified tumor cells both

in vitro

and

in vivo

we observed that the PA-STK ovarian tumor cells were

sensitive to γ-irradiation, completely abolishing their ability to induce bystander killing of unmodified tumor

cells. In contrast, TK-modified human and mouse mesothelioma cells were found to retain their

in vitro

and

vivo

bystander killing effect after γ-irradiation. Characterisation of tumor cell death showed that PA-STK cells

underwent pyknosis (necrosis) after γ-irradiation. These results suggest that PA-STK cells are not suitable for

clinical application of suicide gene therapy of cancer, as lethal γ-irradiation (100Gy) interferes with their by-

stander killing activity. However, the human mesothelioma cell line CRL-5830-TK retained its bystander killing

potential after exposure to similarly lethal γ-irradiation (100Gy). CRL-5830 may therefore be a suitable vehicle

for HSV-TK suicide gene therapy. This study highlights the diversity among tumor cell lines and the careful con-

siderations needed to find the optimal tumor cell line for this type of whole cell tumour vaccination.

Arch Gen Intern Med 2019, Volume 3 | DOI: 10.4066/2591-7951-C2-027