Immunisation with autologous glioma cells transfected with IFN-g gene significantly prolongs survival in GBM-patients older than 50 years.
Salford LG1,2, Ask E3, Siesjö P1,2 S 1,2, Skagerberg G1,2 Bauréus Koch C 4,2, Blennow C1,2,Darabi A1,2, Elfgren C5, Englund E6, Janelidze S1,2, Larsson E-M7, Lilja Å1, Persson BRR4,2, Rydelius A1,3, Strömblad S1,2,Visse E1,2 and Widegren B7.
Dept. of Neurosurgery1 The Rausing Laboratory2, Depts of Neurology3, Medical Radiation Physics4, Neuropsychology5 Neuropathology6, Neuroradiology7 and Tumour Immunology8, Lund University, Lund, Sweden
Based upon earlier experimental work by our group, we have completed the first part of a human immuno-gene therapy study in patients operated for a glioblastoma multiforme.
The goal is to ascertain whether immunisation with autologous tumour cells expressing gene-sequences for human IFN-g: is safe for the patients, gives rise to an immunological response and adds any beneficial effect to conventional therapy. This report is based upon the completed treatment of our first nine patients.
Patients aged 50 to 69 years, in which at least 80% of the GBM is resected during neurosurgery, can be included in the study. The tumour cells are cultured in a special Clinical Transduction Laboratory. When at least 40 million cells, karyotyped as malignant, are collected, the immunisations are given 3-weekly, repeated at least 4 and at most 10 times.
The immunisation takes place in the dermis of the upper arm. Seven days after each immunisation, a skin biopsy is taken from the centre of one of the injection sites. The composition of the cellular infiltration in the skin is studied by markers for T lymphocytes (CD3); Helper cells, subset of T cells (CD4); Cytolytic T-cells, subset of T cells (CD8); Natural killer cells (CD16) and B lymphocytes, B cells (CD20). Also the expression of cytokines for functional T cell subsets are studied: IL-2, IL-4, IL-10, IL-12, IL-18, TNF-a, TNF-, IFN-g and TGF- b 1, 2 and 3.
Peripheral blood is sampled both before and after operation and also after each immunisation event. Co-culture of this blood with tumour cells from the patient allows for a selection of T-cells that can recognise tumour-specific antigens.
The patients are followed regularly with neurological, neuropsychological and MRI examinations.
Results from the first human treatments show that the method is safe for the patients and that it gives rise to positive DTH reactions and an increase of infiltrative CD8+ and CD4+ T-cells at the site of immunisation. Seven patients received 10 immunisations, 1 had eight and 1 six immunisations.
The material is small, but out of 9 patients, 3 survived for 19.5, 22 and 26.5 months and one is still alive after 23 months with a minor tumour burden. The mean survival time of these 9 patients (mean age 62 y.) is 16.2 months to be compared to the 10.4 months survival (p 0,03, Mann-Whitney one-sided test) of the 13 patients (mean age 60 y.), included in the study but where the cells did not grow sufficiently well in the cultures to make immunisation possible.
| Period | 2005 May 5 |
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| Event type | Workshop |
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| Location | Edinburgh, United KingdomShow on map |
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- Medical and Health Sciences