Applied physiology of IGF-I: case reports of gene therapy of malignant tumors especially glioma.

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Published Sep 15, 2018
DOI: https://doi.org/10.18103/mra.v6i9.1809

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Main Article Content

J. Trojan
1. Lab. Legrand S.A., Colombia, and Paris XI University, France; 2. ICGT - International Cancer Gene Therapy Found., Bogota/Paris, Colombia and France; 3. International Foscal Clinic & UNAB, Floridablanca, Colombia
H. Kasprzak
1. ICGT - International Cancer Gene Therapy Found., Bogota/Paris, Colombia and France; 2. Collegium Medicum, UMK University, Bydgoszcz, Poland
M. Bierwagen
UMK University, Bydgoszcz, Poland
G. Quintero
1. ICGT - International Cancer Gene Therapy Found., Bogota/Paris, Colombia and France; 2. International Foscal Clinic & UNAB, Floridablanca, Colombia
A. Guzman
ICGT - International Cancer Gene Therapy Found., Bogota/Paris, Colombia and France
R. Santander O. Abuchaibe
International Foscal Clinic & UNAB, Floridablanca, Colombia
C. Rojas
International Foscal Clinic & UNAB, Floridablanca, Colombia
Y-C. Lone
Lab. Legrand S.A., Colombia, and Paris XI University, France
T. Popiela
Collegium Medicum, Jagiellonian University, Cracow, Poland
P. Penagos
INC - National Cancer Institute, Bogota, Colombia
Y. X. Pan
CWRU University, Cleveland, OH, USA
M. C. Noguera
La Sabana University, Chia/Bogota, Colombia
A. Ayala
Distrital University, Bogota, Colombia
A. Ly
Lab. Legrand S.A., Colombia, and Paris XI University, France
A. Shevelev
Lab. Cell Engineering, Cardiology Institute, Moscow, Russia
E. A. Paez
Kennedy Hospital, Bogota, Colombia
O. Gutierrez
Kennedy Hospital, Bogota, Colombia
D. D. Anthony
CWRU University, Cleveland, OH, USA
I. Briceno
1. ICGT - International Cancer Gene Therapy Found., Bogota/Paris, Colombia and France; 2. La Sabana University, Chia/Bogota, Colombia
A. Trojan
1. ICGT - International Cancer Gene Therapy Found., Bogota/Paris, Colombia and France; 2. Faculty of Medicine, FUJNC University, Bogota, Colombia

Abstract

Abstract


Introduction: Certain specific antigens, which behave as oncoproteins, are present in normal fetal/neonatal brain development, and are absent from mature brain tissues: among them, growth factors, especially insulin-like growth factor type I (IGF-I). When IGF-I reappears in the mature brain, this growth factor is over expressed in neoplastic glia, participating in the development of the most common human brain malignant tumor, glioblastoma multiforme, which is invariably fatal. Targeting the IGF-I system has emerged as a useful method to reduce glial malignant development.


Methodology: In practice, in case-control study, when human glioblastoma cells, and comparatively studied primary hepatocarcinoma and colon adenocarcinoma cells derived from cancer biopsy, are transfected in vitro with vectors expressing either IGF-I antisense RNA or inducing IGF RNA-DNA triple helix, the synthesis of IGF-I is stopped on translation or transcription levels, respectively (anti – gene strategy). Three cancer groups of two patients each, cancer stage I, after surgery and radiotherapy, were injected using antisense / triple helix ‘’vaccines’’ of 1 million irradiated cells. The control groups received injected placebo.


Results: Down regulation in the expression of IGF-I coincides with the reappearance of B7 and MHC class I antigens at the surface of transfected cells (immunogenicity). When injected subcutaneously, the transfected cancer cells, “vaccines”, initiate an immune reaction involving CD8+ lymphocytes, followed by tumor regression. The glioblastoma patients treated by classical surgery and radiotherapy, were “vaccinated” by three successive injections. The median survival of treated patients was 21 months (current progress in treatment of this disease involves an increase in medium survival from 8-11 months to an average of 15 months, using a chemotherapy). Using the same strategy, the patients with liver carcinoma and colon adenocarcinoma were comparatively treated. The obtained immune anti-tumor response mediated by TCD8 was similar to that of glioblastoma patients.


Conclusion: The cellular immunogene therapy using anti - gene approach constitutes one of the current efficient therapies of glioblastoma and other malignancies expressing IGF-I. The described methodology applied in Europe, and previously in the USA for glioblastoma treatment, is introduced now in university hospitals of Colombia (Bogota).

Keywords: IGF-I, glioma, antisense, immunogene therapy, TCD8

Article Details

How to Cite
TROJAN, J. et al. Applied physiology of IGF-I: case reports of gene therapy of malignant tumors especially glioma.. Medical Research Archives, [S.l.], v. 6, n. 9, sep. 2018. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1809>. Date accessed: 13 nov. 2024. doi: https://doi.org/10.18103/mra.v6i9.1809.
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Issue
Vol 6 No 9 (2018): Vol.6 Issue 9, September 2018
Section
Research Articles

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References

1. Hajeri-Germond M, Trojan A, Naval J, et al. Diagnostic of CNS neoplasia – AFP and IGF-I targets. In: Trojan J, ed. Brain: from development to neoplasia and gene therapy solution. Vol.1. 1st ed. Saarbrucken, Germany: Lambert Academic Publishers; 2017/18:76-94.
2. Le Roith D. The insulin-like growth factor system. Exp Diabesity Res. 2003;4:205-212.
3. Baserga R. The Insulin-Like Growth Factor-I Receptor as a target for cancer therapy. Expert Opinion Ther Targets. 2005;9:753-768.
4. Pollak MN, Schernhammer ES, Han-kinson SE. Insulin-like growth factors and neoplasia. Nat Rev Cancer. 2004;4:505–518.
5. Trojan J, Cloix J-F, Ardourel M, et al. IGF-I biology and targeting in malignant glioma. Neurosci. 2007;45(3):795-811.
6. Rabinovsky E D. The multifunctional role of IGF-1 in peripheral nerve re-generation. Neurol Res. 2004;26:204-210.
7. Trojan A, Aristizabal B, Jay LM, et al. Testing of IGF-I biomarker in an ethical context. Adv Modern Onco Res. 2016;2(4): doi: 10.18282/amor: v2:i4.58; 2016a
8. Bondy C A, Werner H, Roberts CTJr, et al. Cellular pattern of insulin-like growth factor-I (IGF-I) and type I IGF receptor gene expression in early organogenesis: comparison with IGF-II gene expression. Mol Endocrinol. 1990;4:1386-1398.
9. Schultz GA, Hahnel A, Arcellana-Panlilio M, et al. Expression of IGF ligand and receptor genes during pre-implantation mammalian develop-ment. Mol Reprod Dev. 1993;35:414-420.
10. Bartlett W P, Li X S, Williams M. Expression of IGF-1 mRNA in the murine subventricular zone during postnatal development. Brain Res Mol Brain Res. 1992;12: 285-291.
11. Wilkins A, Chandran S, Compston A. A role for oligodendrocyte-derived IGF-1 in trophic support of cortical neurons. Glia.2001;36:48-57.
12. Porcu, P, Rubini, M. The role of the IGF-I receptor in the growth and transformation of mammaliancells. Cell Prolif. 1994;27:63-71.
13. Adhami V M, Afaq F, Mukhtar H. Insulin-like growth factor-I axis as a pathway for cancer chemoprevention. Clin Cancer Res. 2006;12:5611-5614.
14. Harding BN, Golden JA. Develop-mental neuropathology. Internat Soc Neuropathol. Basel, Suiss 2004.
15. Esiri M, Perl D, ed. Oppenheimer’s diagnostic neuropathology. 3rd ed, FL: CRC Press; 2006.
16. Love S, Arie Perry A, Ironside J, Budka H, ed. Greenfield's Neuropa-thology. 9th ed, NY: CRC Press; 2015.
17. Pfrieger FW. Role of glia in synapse development. Curr Opin Neurobiol. 2002;12:486-490.
18. Barres BA. What is a glial cell?. Glia. 2003;43: 4-5.
19. Hofer T, Venance L, Giaume C. Con-trol and plasticity of intercellular cal-cium waves in astrocytes: a modeling approach. J Neurosci. 2002;22:4850-4859.
20. Stupp R, Hegi ME, Neyns B, et al. Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomid maintenance therapy in patients with newly diagnosed glioblastoma. J Clin Oncol. 2010; 28(16): 2712-2718.
21. Wen PY, Yung WK, Lamborn KR et al. Phase I/II study of imatinib mesy-late for recurrent malignant gliomas: Norty American Brain Tumor Con-sortium Study 99-08. Clin Cancer Res. 2006;12:4899-4907.
22. Pan Q, Luo X, Chegini N. Blocking neuropilin-1 function has an additive effect with anti VEGF to inhibit tu-mor growth. Cancer Cell. 2007;11(1): 53-67.
23. Kjaergaard J, Wang LX, Kuriyama H, et al. Active immunotherapy for ad-vanced intracranial murine tumors by using dendritic cell-tumor cell fusion vaccines. J Neurosurg. 2005;103: 156-164.
24. Wikipedia – Encyclopedia, Gene therapy – History 1990s
25. Rubenstein, JL, Nicolas JF, Jacob F. Construction of a retrovirus capable of transducing and expressing genes in multipotential embryonic cells. Proc Natl Acad Sci USA. 1984;81:7137-7140.
26. Helene C. Control of oncogene expression by antisense nucleic acids. Euro J Cancer. 1994; 30A: 1721-1726.
27. Trojan J, Johnson TR, Rudin SD, et al. Gene therapy of murine teratocar-cinoma: separate functions for insu-lin-like growth factors I and II in im-munogenicity and differentiation of multipotential embryonic cells. Proc Natl Acad Sci USA. 1994; 91:6088-6092.
28. Ellouk-Achard S. Djenabi GA, De Oliveira, et al. Induction of apoptosis in rat hepatoma cells by expression of IGF-I antisense cDNA. J Hepa-tol.1998;29:807-818.
29. Trabado S, Van Binh PN, Martin C, et al. Stimulation of anti-melanoma immune effectors via modified tumor cells exhibiting inhibited IGF-I and low CD9. Biomed & Pharmacother. 2007;61(8):494-498.
30. Djavan W, Aldert M, Seitz C, et al. Insulin-like growth factors and pros-tate cancer. World J Urol. 2001;19(4): 225-233.
31. Wu Y, Yakar S, Henninghausen L, et al. Circulating Insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res. 2002;62:1030-1035.
32. Trojan J, Johnson TR, Rudin SD, et al. Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA. Science. 1993;259:94-97.
33. Lafarge-Frayssinet C, Duc HT, Sara-sin A, et al. Antisense IGF-I transfer into rat hepatomacell line inhibits tu-morigenesis by modulating MHC-I. Cancer Gene Ther. 1997;4:276-285.
34. Shevelev A, Burfeind P, Schulze E, et al. Potential triple helix-mediated in-hibition of IGF-I gene expression sig-nificantly reduces tumorigenicity of glioblastoma in an animal model. Cancer Gene Ther. 1997;4:105-101.
35. DeAngelis LM. Brain tumors. N Engl J Med. 2001;344:114-123.
36. Fakhrai H, Mantil JC, Liu L, et al. Phase I clinical trial of a TGF-beta antisense-modified tumor cell vaccine in patients with advanced glioma. Cancer Gene Ther. 2006; 13(12): 1052-1060.
37. Schlingensiepen KH, Schlingensiepen R, Steinbrecher A, et al. Targeted tumor therapy with the TGF-beta2 antisense compound AP 12009. Cytokine Growth Factor Rev. 2006;17:129-139.
38. Schlingensiepen KH, Fischer-Blass B, Schmaus S, et al. Antisense therapeutics for tumor treatment: the TGF-beta2 inhibitor AP 12009 in clinical development against malignant tumors. Recent Results Cancer Res. 2008;177:137-150.
39. Hau P, Jachimczak R, Schlingensie-pen KH, et al. Inhibition of TGF-beta2 with AP 12009 in recurrent ma-lignant gliomas: from preclinical to phase I/II studies. Oligonucleotides. 2007;17(2); 201-212.
40. Anthony DD. Ex vivo and in vivo IGF-1 antisense RNA strategies for treatment of cancers in humans [ab-stract]. Cancer Gene Ther. 1997; 2:322.
41. Matthew L, Saiter B , Bhardwag N. Dendritic cells acquire antigen from apoptotic cells and induce class I re-stricted CTL. Nature. 1998;392:86-89.
42. Upegui-Gonzalez LC, Ly A, Sierzega M, et al. IGF-I triple helix strategy in hepatoma Treatment. Hepato/ Ga-stroenterol. 2001;48:660-666.
43. Schwartz RH. Costimulation of T lymphocytes: the role of CD28, CTLA-4 and B7/BBI in interleukin-2 production and immunotherapy. Cell. 1992;71:1065-1068.
44. Kindt TJ, Goldsby RA, Osborne BA, ed. Kuby Immunology. NY: WH Freeman and Co; 2007.
45. Beckner ME, Gobbel GT, Abounader R. Glycolytic glioma cells with ac-tive glycogen synthase are sensitive to PTEN and inhibitors of PI3K and gluconeogenesis. Lab Investigat. 2005;85(12):1457–1470.
46. Trojan J, Pan YX, Wei MX, et al. Methodology for anti - gene anti - IGF-I therapy of malignant tumours. Chemother Res Pract. doi:10.1155/ 2012/721873; 2011/2012
47. Pan Y, Trojan J, Guo Y, Anthony DD. Rescue of MHC-1 antigen processing machinery by down-regulation in expression of IGF-I in human glioblastoma cells. PLoS ONE. 2013;8:ID: e58428.
48. Premkumar DR, Arnold B, Jane EP, Pollack IF. Synergistic interactions between 17 AAG and phosphatidyli-nositol 3-kinase inhibition in human malignant glioma cells. Mol Carcinogene. 2006;45:47-59.
49. Ardourel M-Y, Blin M, Moret J-L, et al. A new putative target for antisense gene therapy of glioma: glycogen synthetase. Cancer Biol Ther. 2007;6(5):719-723.
50. Trojan J, ed. Cancer immunogene therapy – case of glioblastoma. Anti – gene anti IGF-I approach. Saarbrucken, Germany: Lambert Academic Publishers; 2017.