Methodology for Anti-Gene Anti-IGF-I Therapy of Malignant Tumours

Author:

Trojan Jerzy123,Pan Yuexin X.4,Wei Ming X.5,Ly Adama1,Shevelev Alexander6,Bierwagen Maciej7,Ardourel Marie-Yvonne8,Trojan Ladislas A.12,Alvarez Alvaro2,Andres Christian9,Noguera Maria C.3,Briceno Ignacio3,Aristizabal Beatriz H.10,Kasprzak Heliodor7,Duc Huynh T.1,Anthony Donald D.4

Affiliation:

1. INSERM U542 and U602, Paul Brousse Hospital, Paris XI University, 16 Avenue. PV Couturier, 94807 Villejuif, France

2. Laboratory of Gene Therapy, Faculty of Medicine, Cartagena's University, Cartagena de Indias, Colombia

3. Faculty of Medicine, La Sabana University, Chia, Autopista Norte de Bogota, Colombia

4. Department of General Medical Sciences, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA

5. Cellvax, Veterinary National School, 7 Avenue General De Gaule, 94704 Maisons Alfort, France

6. Laboratory of Cell Engineering, Cardiology Institute, Moscow University, Cherepkowskaya Street, Moscow 12 1552, Russia

7. Department of Gene Therapy and Department of Neurosurgery, Collegium Medicum, Nicolas Copernic University, M. Curie Sklodowska Street, 85067 Bydgoszcz, Poland

8. Laboratory of Neurobiology, Faculty of Science, Orleans' University, 45067 Orleans, France

9. INSERM U930, Bretonneau Hospital, Tours' University, 2 Bd Tonnelle, 37044 Tours, France

10. Laboratory of Molecular Diagnostic, Pablo Tobon Uribe Hospital, UPB University, Medellín, Colombia

Abstract

The aim of this study was to establish the criteria for methodology of cellular “anti-IGF-I” therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix expression vectors. The prepared cell “vaccines” should it be in the case of glioblastomas or other tumours, have shown a change of phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8+ and CD8+28+ molecules and a switch from CD8+11b+ to CD8+11. All cancer patients were supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria for “anti-IGF-I” strategy: characteristics sine qua non of injected “vaccines” (cloned cells IGF-I(−) and MHC-I(+)) and of PBL cells (CD8+ increased level).

Publisher

Hindawi Limited

Subject

Pharmacology (medical),General Pharmacology, Toxicology and Pharmaceutics,Oncology

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