The toxic effect of radioactive substrate of HSV1-TK on antigen specific T cells during noninvasive imaging



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Abstract

Using the ability of genetically modified herpes simplex virus thymidine kinase expressing cells to specifically accumulate radioactively labeled analogs of gancyclovir, we analyzed the distribution of encephalitogenicT cells during prodromal phase of transfer EAE and toxic effect of this accumulation on functional activity ofT cells in vitro and in vivo. Though gamma scanning was not sensitive enough for detection of encephalitogenic T cells in organs with low concentration of them we confirmed that spleen is one of the most important organs forT cells during EAE development. Moreover, we have found a toxic effect of radioactively labeled analogs of GCV on effectorT cells leading to inhibition of proliferation in vitro and significant attenuation of EAE symptoms in vivo. Thus, widely clinically and experimentally applying methods of noninvasive in vivo imaging of adaptive transferred T cells with application of radioactive substrate, as we have shown, can lead to attenuation of functional activity of these cells and accordingly to an inefficiency of therapy or wrong interpretation of the obtained data.

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References

  1. Moolten F.L. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy // Cancer Res. 1986. (Oct.).Vol. 46 (10). P. 5276-5281.
  2. Ilsley D.D., Lee S.H., Miller W.H., Kuchta R.D. Acyclic guanosine analogs inhibit DNA polymerases alpha, delta, and epsilon with very different potencies and have unique mechanisms of action // Biochemistry. 1995 (Feb 28). Vol. 34 (8). P. 2504-2510.
  3. Fillat C., Carrio M., Cascante A., Sangro B. Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene / Ganciclovir system: fifteen years of application // Cur. Gene Ther. 2003 (Feb.). Vol. З (1). P. 13-26. (Rev.)
  4. Kolb H.J., Schmid C., Barrett A.J., Schendel D.J. Graft-versus-leukemia reactions in allogeneic chime- 'ras // Blood. 2004 (Feb 1). Vol. 103 (3). P. 767-776; Epub. 2003 (Sep 4). (Rev.)
  5. Kolb H.J., Mittermtiller J., Clemm C. et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients // Blood. 1990 (Dec 15). Vol. 76 (12). P. 2462-2465.
  6. Ciceri F., Bonini C., Gallo-Stampino C., Bordignon C. Modulation of GvHD by suicide-gene transduced donor T lymphocytes: clinical applications in mismatched transplantation//Cytotherapy. 2005. Vol. 7 (2). P. 144- 149. (Rev.)
  7. Painter R.G., Lanson N.A. Jr., Jin Z., Park F., Wang G. Conditional expression of a suicide gene by the telomere reverse transcriptase promoter for potential post- therapeutic deletion of tumorigenesis // Cancer Sci. 2005 (Sep). Vol. 96 (9). P. 607-613.
  8. Sakaguchi S., Sakaguchi N., Shimizu J. et al. Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance // Immunol. Rev. 2001 (Aug). Vol. 182. P. 18-32. (Rev.)
  9. Cohen J.L., Boyer O., Klatzmann D. Would suicide gene therapy solve the ‘T-cell dilemma’ of allogeneic bone marrow transplantation? // Immunol. Today. 1999 (Apr). Vol. 20 (4). P. 172-176. (Rev.)
  10. Tjuvajev J.G., Stockhammer G., Desai R. et al. Imaging the expression of transfected genes in vivo // Cancer Res. 1995 (Dec 15). Vol. 55 (24). P. 6126-6132.
  11. Tjuvajev J.G., Finn R., Watanabe K. et al. Noninvasive imaging of heipes virus thymidine kinase gene transfer and expression: a potential method for monitoring clinical gene therapy // Cancer Res. 1996 (Sep 15). Vol. 56 (18). P. 4087-4095.
  12. Tjuvajev JG, Avril N, Oku T. et al. Imaging herpes virus thymidine kinase gene transfer and expression by positron emission tomography // Cancer Res. 1998 (Oct 1). Vol. 58 (19). P. 4333-4341.
  13. Larson S.M., Tjuvajev J., Blasberg R. Triumph over mischance: a role for nuclear medicine in gene therapy //J. Nucl. Med. 1997 (Aug). Vol. 38 (8). P. 1230-1233. (Rev.)
  14. Koehne G., Doubrovin M., Doubrovina E. et al. Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes // Nat. Biotechnol. 2003 (Apr). Vol. 21 (4). P. 405-413; Epub. 2003 (Mar 24).
  15. Zanzonico P., Koehne G., Gallardo H.F. et al. [1311] FIAU labeling of genetically transduced, tumor-reactive lymphocytes: cell-level dosimetry and dose-dependent toxicity// Eur. J. Nucl. Med. Mol. Imaging. 2006 (Sep). Vol. 33 (9). P. 988-997; Epub. 2006 (Apr 11).
  16. Doubrovin M.M., Doubrovina E.S. et al. In vivo imaging and quantitation of adoptively transferred human antigen-specific T cells transduced to express a human norepinephrine transporter gene // Cancer Res. 2007 (Dec 15). Vol. 67 (24). P. 11959-11969.
  17. Fltigel A., Willem M., Berkowicz T, Wekerle H. Gene transfer into CD4+ T lymphocytes: green fluorescent protein-engineered, encephalitogenic T cells illuminate brain autoimmune responses //Nat. Med. 1999 (Jul). Vol. 5 (7). P. 843-847.
  18. Alauddin M.M., Conti P.S. Synthesis and preliminary evaluation of 9-(4-[ 18F]-fluoro-3-hydroxymethylbutyl )guanine ([18FJFHBG): a new potential imaging agent for viral infection and gene therapy using PET // Nucl. Med. Biol. 1998 (Apr). Vol. 25 (3). P. 175-180.
  19. Gambhir S.S., Bauer E., Black M.E. et al. A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography // Proc. Natl. Acad. Sci. USA. 2000 (Mar 14). Vol. 97 (6). P. 2785-2790.
  20. Odoardi F., Kawakami N., Li Z. et al. Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis // Proc. Natl. Acad. Sci. USA. 2007 (Jan 16). Vol. 104 (3). P. 920-925; Epub. 2007 (Jan 9).

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Copyright (c) 2010 Nosov M.A., Anton M., Weber W., Barabanova S.V., Wekerle H., Korneva E.A., Fluegel A.

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