Radiation sterilisation of cultured human brain tumour cells for clinical immune tumour therapy

Bauréus-Koch, C; Nyberg, Gudrun; Widegren, Bengt; Salford, Leif G.; Persson, Bertil

doi:10.1038/sj.bjc.6601467

Cited by 6 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is particularly relevant to the development of γ-irradiated cancer vaccines such as GVAX, which is currently in clinical trials [ 43 ]. DSs reported are typically between 35 [ 44 ] and 100 Gy [ 45 ]. The radiosensitivity of mammalian cells is explained by a considerably larger genome than viruses and bacteria.…”

Section: Discussionmentioning

confidence: 99%

Sterility of gamma-irradiated pathogens: a new mathematical formula to calculate sterilizing doses

Singleton

David

Davies

et al. 2020

Journal of Radiation Research

View full text Add to dashboard Cite

In recent years there has been increasing advocacy for highly immunogenic gamma-irradiated vaccines, several of which are currently in clinical or pre-clinical trials. Importantly, various methods of mathematical modelling and sterility testing are employed to ensure sterility. However, these methods are designed for materials with a low bioburden, such as food and pharmaceuticals. Consequently, current methods may not be reliable or applicable to estimate the irradiation dose required to sterilize microbiological preparations for vaccine purposes, where bioburden is deliberately high. In this study we investigated the applicability of current methods to calculate the sterilizing doses for different microbes. We generated inactivation curves that demonstrate single-hit and multiple-hit kinetics under different irradiation temperatures for high-titre preparations of pathogens with different genomic structures. Our data demonstrate that inactivation of viruses such as Influenza A virus, Zika virus, Semliki Forest virus and Newcastle Disease virus show single-hit kinetics following exposure to gamma-irradiation. In contrast, rotavirus inactivation shows multiple-hit kinetics and the sterilizing dose could not be calculated using current mathematical methods. Similarly, Streptococcus pneumoniae demonstrates multiple-hit kinetics. These variations in killing curves reveal an important gap in current mathematical formulae to determine sterility assurance levels. Here we propose a simple method to calculate the irradiation dose required for a single log10 reduction in bioburden (D10) value and sterilizing doses, incorporating both single- and multiple-hit kinetics, and taking into account the possible existence of a resistance shoulder for some pathogens following exposure to gamma-irradiation.

show abstract

Section: Discussionmentioning

confidence: 99%

Sterility of gamma-irradiated pathogens: a new mathematical formula to calculate sterilizing doses

Singleton

David

Davies

et al. 2020

Journal of Radiation Research

View full text Add to dashboard Cite

show abstract

“…Tumour tissue obtained at surgery was cultured in vitro and regularly karyotyped until the cells exhibited an abnormal karyotype. Then the cultivated cells were transduced using an adenoviral vector carrying the IFN-γ Human gene as well as the gene for the Green Fluorescent Protein and subsequently irradiated with 100 Gy to prevent a further growth in vivo [23,24].…”

Section: Cell Culturementioning

confidence: 99%

A Story of Immunization with Autologous IFN-γ Secreting Glioma Cells in Patients with Glioblastoma Multiforme is Safe and Prolongs Both Overall and Progress Free Survival

G.¹,

Siesjö²,

Skagerberg³

et al. 2023

Glioblastoma - Current Evidence

View full text Add to dashboard Cite

The study was a non-randomized controlled phase I-II trial to study were to ascertain the safety, feasibility and efficacy of immunotherapy with autologous IFN-γ transfected tumour cells in patients with glioblastoma multiforme. Autologous tumour cells harvested during surgery were cultured and transduced with the human IFN-γ gene. Irradiated cells were administered as intradermal immunizations every third week. Endpoints for safety were records of toxicity and adverse events, for feasibility the per cent of treated patients out of eligible patients and time to treatment and for clinical efficacy overall survival (OS) and progress free survival (PFS). Eight eligible patients, between 50 and 69 years, were immunized between 8 and 14 times after treatment with surgery and radiotherapy without adverse events or toxicity. Neurological status and quality of life were unchanged during immunotherapy. The immunized patients had a significantly (p < 0.05) longer median overall survival (488 days, 16.1 months than a matched control group of nine patients treated with only surgery and radiotherapy (271 days, 9.0 months). The prolongation of survival was also significant compared to all GBM treated at the same institution during the same period and published control groups within the same age cohort.

show abstract

RETRACTED: Radiation-enhanced hepatocyte growth factor secretion in malignant glioma cell lines

Chu

Zhu

et al. 2007

Surgical Neurology

View full text Add to dashboard Cite

Radiation sterilisation of cultured human brain tumour cells for clinical immune tumour therapy

Cited by 6 publications

References 18 publications

Sterility of gamma-irradiated pathogens: a new mathematical formula to calculate sterilizing doses

Sterility of gamma-irradiated pathogens: a new mathematical formula to calculate sterilizing doses

A Story of Immunization with Autologous IFN-γ Secreting Glioma Cells in Patients with Glioblastoma Multiforme is Safe and Prolongs Both Overall and Progress Free Survival

RETRACTED: Radiation-enhanced hepatocyte growth factor secretion in malignant glioma cell lines

Contact Info

Product

Resources

About