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Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model

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Abstract

Purpose: We investigated the effect of intraoperative intrasplenic or subcutaneous vaccination with modified tumor cells on tumor progression in a mouse model. Methods: Pre-established B16 melanomas on C57/Bl6 mice were surgically removed; mice were vaccinated intraoperatively with B16 cells transfected with an IL-12-encoding pRSC construct, the empty plasmid, or B16 frozen cells. Cells were given either intrasplenically or subcutaneously. Intrasplenic effects of vaccination were examined along with survival data. Mice without tumor recurrence underwent a second tumor implantation. Results: Animals administered IL-12 pRSC cells showed significant alterations in the spleen, such as higher percentages of (activated) CD4+ and CD8+ T cells and tumor-specific CD4+ T cells among splenocytes. The tumor recurrence rate after resection ranged from 13 to 36%. Cases with recurrent tumors in particular benefited in all therapy groups, resulting in enhanced (tumor-free) survival, reduced tumor growth and lower metastasis rates. Following macroscopic complete tumor resection, the optimum outcome resulted from vaccination with IL-12 pRSC cells into the spleen and subcutaneously administered frozen cells. Survival times were enhanced in all therapy groups after tumor reimplantation, although results were not significant. Conclusions: Intraoperative whole-cell vaccination with autologous tumor cells yields promising data, and could be considered as a future option in adjuvant cancer therapy.

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References

  • Burns VE, Carroll D, Ring C, Drayson M (2003) Antibody response to vaccination and psychosocial stress in humans: relationships and mechanisms. Vaccine 21:2523–2534

    Article  PubMed  CAS  Google Scholar 

  • Cayeux S, Qin Z, Dorken B, Blankenstein T (2001) Decreased generation of anti-tumor immunity after intrasplenic immunization. Eur J Immunol 31:1392–1399

    Article  PubMed  CAS  Google Scholar 

  • Cheng L, Ziegelhoffer PR, Yang NS (1993) In vivo promoter activity and transgene expression in mammalian somatic tissues evaluated by using particle bombardment. Proc Natl Acad Sci USA 90:4455–4459

    Article  PubMed  CAS  Google Scholar 

  • Cohen S, Miller GE, Rabin BS (2001) Psychological stress and antibody response to immunization: a critical review of the human literature. Psychosom Med 63:7–18

    PubMed  CAS  Google Scholar 

  • Decken K, Kohler G, Palmer-Lehmann K, Wunderlin A, Mattner F, Magram J, Gately MK, Alber G (1998) Interleukin-12 is essential for a protective Th1 response in mice infected with cryptococcus neoformans. Infect Immun 66:4994–5000

    PubMed  CAS  Google Scholar 

  • Dietrich A, Kraus K, Brinckmann U, Friedrich T, Muller A, Liebert UG, Schonfelder M (2002) Complex cancer gene therapy in mice melanoma. Langenbecks Arch Surg 387:177–182

    Article  PubMed  Google Scholar 

  • Flad HD, Gemsa D (1999) Zytokine. In: Gemsa D, Kalden G (eds) Immunologie, 3rd edn. Thieme Verlag Heidelberg, NY, pp 45–67

    Google Scholar 

  • Heinzerling L, Dummer R, Pavlovic J, Schultz J, Burg G, Moelling K (2002) Tumor regression of human and murine melanoma after intratumoral injection of IL-12-encoding plasmid DNA in mice. Exp Dermatol 11:232–240

    Article  PubMed  CAS  Google Scholar 

  • Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, Kandemir A, Lee PP, Schuler G, Knop J, Enk AH (2001) A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 93:243–251

    Article  PubMed  CAS  Google Scholar 

  • Kundig TM (2000) Methods for increasing the immunogenicity of vaccines. Schweiz Rundsch Med Prax 89:1477–1484

    PubMed  CAS  Google Scholar 

  • Kundig TM, Bachmann MF, DiPaolo C, Simard JJ, Battegay M, Lother H, Gessner A, Kuhlcke K, Ohashi PS, Hengartner H, et al (1995) Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science 268:1343–1347

    Article  PubMed  CAS  Google Scholar 

  • Mahvi DM, Sondel PM, Yang NS, Albertini MR, Schiller JH, Hank J, Heiner J, Gan J, Swain W, Logrono R (1997) Phase I/IB study of immunization with autologous tumor cells transfected with the GM-CSF gene by particle-mediated transfer in patients with melanoma or sarcoma. Hum Gene Ther 8:875–891

    PubMed  CAS  Google Scholar 

  • Maloy KJ, Erdmann I, Basch V, Sierro S, Kramps TA, Zinkernagel RM, Oehen S, Kundig TM (2001) Intralymphatic immunization enhances DNA vaccination. Proc Natl Acad Sci USA 98:3299–3303

    Article  PubMed  CAS  Google Scholar 

  • Mesa C, Fernandez LE (2004) Challenges facing adjuvants for cancer immunotherapy. Immunol Cell Biol 82:644–650

    Article  PubMed  CAS  Google Scholar 

  • Miller GE, Cohen S, Pressman S, Barkin A, Rabin BS, Treanor JJ (2004) Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body? Psychosom Med 66:215–223

    Article  PubMed  Google Scholar 

  • Mocellin S, Mandruzzato S, Bronte V, Lise M, Nitti D (2004) Part I: Vaccines for solid tumours. Lancet Oncol 5:681–689

    Article  PubMed  CAS  Google Scholar 

  • Nishitani MA, Sakai T, Ishii K, Zhang M, Nakano Y, Nitta Y, Miyazaki J, Kanayama HO, Kagawa S, Himeno K (2002) A convenient cancer vaccine therapy with in vivo transfer of interleukin 12 expression plasmid using gene gun technology after priming with irradiated carcinoma cells. Cancer Gene Ther 9:156–163

    Article  PubMed  CAS  Google Scholar 

  • Novakovic S, Knezevic M, Golouh R, Jezersek B (1999) Transfection of mammalian cells by the methods of receptor mediated gene transfer and particle bombardment. J Exp Clin Cancer Res 18:531–536

    PubMed  CAS  Google Scholar 

  • Ochsenbein AF (2005) Immunological ignorance of solid tumors. Springer Semin Immunopathol 27:19–35

    Article  PubMed  Google Scholar 

  • Rakhmilevich AL, Timmins JG, Janssen K, Pohlmann EL, Sheehy MJ, Yang NS (1999) Gene gun-mediated IL-12 gene therapy induces antitumor effects in the absence of toxicity: a direct comparison with systemic IL-12 protein therapy. J Immunother 22:135–144

    Article  PubMed  CAS  Google Scholar 

  • Schirrmacher V (1995a) Biotherapy of cancer. Perspectives of immunotherapy and gene therapy. J Cancer Res Clin Oncol 121:443–451

    Article  CAS  Google Scholar 

  • Schirrmacher V (1995b) Tumor vaccine design: concepts, mechanisms, and efficacy testing. Int Arch Allergy Immunol 108:340–344

    Article  CAS  Google Scholar 

  • Schirrmacher V (2001) T-cell immunity in the induction and maintenance of a tumour dormant state. Semin Cancer Biol 11:285–295

    Article  PubMed  CAS  Google Scholar 

  • Stockmar C (2004) Vakzination mit verschiedenen auch gentechnisch modifizierten autologen Tumorzellen in die Milz im Maus Tumormodell. Thesis, Leipzig University, Leipzig

  • Schirrmacher V (2005) Clinical trials of antitumor vaccination with an autologous tumor cell vaccine modified by virus infection: improvement of patient survival based on improved antitumor immune memory. Cancer Immunol Immunother 54:587–597

    Article  PubMed  CAS  Google Scholar 

  • Storni T, Kundig TM, Senti G, Johansen P (2005) Immunity in response to particulate antigen-delivery systems. Adv Drug Deliv Rev 57:333–355

    Article  PubMed  CAS  Google Scholar 

  • Sun Y, Jurgovsky K, Moller P, Alijagic S, Dorbic T, Georgieva J, Wittig B, Schadendorf D (1998) Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Ther 5:481–490

    Article  PubMed  CAS  Google Scholar 

  • Vogl A, Sartorius U, Vogt T, Roesch A, Landthaler M, Stolz W, Becker B (2005) Gene expression profile changes between melanoma metastases and their daughter cell lines: implication for vaccination protocols. J Invest Dermatol 124:401–404

    Article  PubMed  CAS  Google Scholar 

  • Wang C, Quevedo ME, Lannutti BJ, Gordon KB, Guo D, Sun W, Paller AS (1999) In vivo gene therapy with interleukin-12 inhibits primary vascular tumor growth and induces apoptosis in a mouse model. J Invest Dermatol 112:775–781

    Article  PubMed  CAS  Google Scholar 

  • White SA, LoBuglio AF, Arani RB, Pike MJ, Moore SE, Barlow DL, Conry RM (2000) Induction of anti-tumor immunity by intrasplenic administration of a carcinoembryonic antigen DNA vaccine. J Gene Med 2:135–140

    Article  PubMed  CAS  Google Scholar 

  • Zhou WZ, Hoon DS, Huang SK, Fujii S, Hashimoto K, Morishita R, Kaneda Y (1999) RNA melanoma vaccine: induction of antitumor immunity by human glycoprotein 100 mRNA immunization. Hum Gene Ther 10:2719–2724

    Article  PubMed  CAS  Google Scholar 

  • Zoller M, Matzku S (1999) Cancer therapy: new concepts on active immunization. Immunobiology 201:1–21

    PubMed  CAS  Google Scholar 

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Correspondence to Arne Dietrich.

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Dietrich, A., Stockmar, C., Aust, G. et al. Intraoperative subcutaneous or intrasplenic vaccination with modified autologous tumor cells leads to enhanced survival in a mouse tumor model. J Cancer Res Clin Oncol 132, 379–388 (2006). https://doi.org/10.1007/s00432-005-0073-5

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  • DOI: https://doi.org/10.1007/s00432-005-0073-5

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