Immune response to green fluorescent protein: implications for gene therapy

Stripecke, Renata; Villacres, M. Del Carmen; Skelton, Dianne C.; Satake, Noriko; Halene, Stephanie; Kohn, Donald B.

doi:10.1038/sj.gt.3300951

Cited by 305 publications

(260 citation statements)

References 33 publications

Supporting

Mentioning

248

Contrasting

Unclassified

Order By: Relevance

“…These data are all the more impressive considering the suggestion from previous work that the GFP protein itself is immunogenic. 26 When GFP-positive SCs were transplanted into SCID mice, 100% of the grafts survived as determined by both fluorescence microscopy and immunohistochemistry for GATA-4 (a marker for SCs). In contrast, the survival of GFP SCs in Balb/c mice was more variable with surviving SCs detected in 50-70% of the allografts.…”

Section: Discussionmentioning

confidence: 99%

Genetically engineered Sertoli cells are able to survive allogeneic transplantation

et al. 2004

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Genetically engineered Sertoli cells are able to survive allogeneic transplantation

et al. 2004

View full text Add to dashboard Cite

“…Previously, it has been shown that eGFP is immunogenic in human, 26 non-human primates 27,28 and in murine models. 29,30 Evidences also suggest immune rejection of transplanted eGFP-positive cells in non-human primate recipients in myeloablative 27 as well as nonablative settings. 28 Hence, using eGFP as a model antigen, herein we show that Lenti-eGFP-transduced DC could effectively process and present the eGFP-derived antigenic peptides to contaminating lymphocytes in DC culture and reproducibly generate CTLs capable of eliminating the eGFP-expressing DCs.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

et al. 2005

View full text Add to dashboard Cite

Genetically modified dendritic cell (DC) vaccines expressing tumor-associated antigens are currently used for cancer immunotherapy. Peripheral blood (PB) monocyte precursors are a relatively convenient source of DCs for use in clinical studies, but are often contaminated by lymphocytes. The current study was conducted to examine the impact of Tlymphocyte contamination on genetically modified DC product. PB monocyte-derived DCs were efficiently transduced (75-95%) with an HIV-1-based self-inactivating lentiviral vector encoding a model antigen, the enhanced green fluorescent protein (eGFP). The lymphocyte-free DC culture transduced with Lenti-eGFP showed stable expression of eGFP without measurable decline in viability. In contrast, the eGFP-positive DCs disappeared rapidly in transduced DC cultures containing lymphocyte contaminants, concurrent with detectable activation and expansion of T-lymphocytes. Upon antigen recall, these T cells elicited major histocompatability complex-restricted antigen-specific cytotoxicity against eGFP-positive autologous DCs and mitogen-stimulated T lymphoblasts, mainly through the perforin-mediated pathway. In summary, this study demonstrate that the relative purity of DC cultures could determine the persistence of gene-modified DC, which may affect the induction of effective immune responses by DC vaccination strategies. Gene Therapy (2005) 12, 259-271.

show abstract

“…It was reported that GFP is an immunogen for C57BL/6 and BALB/c mice in tumor studies (Gambotto et al, 2000;Stripecke et al, 2001). In contrast, others have failed to reproduce these findings (Denaro et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Vaccination with leukemia cells expressing cell-surface-associated GM-CSF blocks leukemia induction in immunocompetent mice

et al. 2006

View full text Add to dashboard Cite

The fundamental basis for immunotherapy of leukemia is that leukemic cells express specific antigens that are not expressed by normal hematopoietic cells. However, the host immune system appears to be tolerant to leukemia cells. To overcome this tolerance, we vaccinated immunocompetent mice with murine leukemia cells (WEHI-3B and BCR-ABL þ 32D cells) transduced with a specifically constructed transmembrane form of granulocytemacrophage colony-stimulating factor (tmGM-CSF). The transduced cells expressed tmGM-CSF on the cellsurface. To determine whether tmGM-CSF-expressing WEHI-3B leukemia cells would prevent leukemia formation as a vaccine, immunocompetent mice (BALB/c and C3H/HEJ) were immunized with lethally irradiated murine leukemia cells expressing cell-surface tmGM-CSF before challenging mice with murine leukemia cells. Two immunocompetent mouse models were investigated, either WEHI-3B cells in BALB/c mice or BCR-ABL þ 32D cells in C3H/HEJ mouse. The results showed that 100% of WEHI-3B/tmGM-CSF-vaccinated BALB/c mice and about 65% of 32D þ BCR-ABL/tmGM-CSFvaccinated C3H/HEJ mice were protected from leukemia after leukemia cell challenge, whereas all non-vaccinated mice succumbed to leukemia. Spleen and marrow cell suspensions from vaccinated mice challenged with WEHI-3B cells lacked detectable GFP þ WEHI-3B cells at 82 days post-challenge. A significant delay of death was observed in C3H/HEJ mice challenged with the very aggressive DA-1 cell line expressing BCR-ABL. Vaccination of mice with WEHI-3B/CD40L cells protected 80% of the mice from the WEHI-3B challenge. Notably, 60% of the WEHI-3B/BALB/c mice were also protected from leukemia when WEHI-3B/tmGM-CSF vaccination was carried out after the leukemia challenge. In order to determine whether cellular immunity is involved in this vaccine-mediated protection, either CD4 þ or CD8 þ T cells were depleted from mice after the WEHI-3B/tmGM-CSF vaccination. The results indicate that CD8 þ T-cells mediated the protective immune response provided by the irradiated tmGM-CSF-expressing WEHI-3B cells.In addition, vaccination of nude mice did not provide protection from WEHI-3B leukemia induction. Importantly, 80% of non-vaccinated mice were also protected from a WEHI-3B cell challenge after receiving spleen cells from vaccinated mice 1 day before challenge with leukemia cells. These results indicate that overexpression of tmGM-CSF on the leukemia cell-surface can enhance the recognition of leukemic cells by CD8 þ T cells, and can either prevent or significantly delay leukemia induction. These findings suggest that injection of irradiated leukemia cells expressing cell-surface-bound GM-CSF has the potential as an immunological approach to treat leukemia.

show abstract

Immune response to green fluorescent protein: implications for gene therapy

Cited by 305 publications

References 33 publications

Genetically engineered Sertoli cells are able to survive allogeneic transplantation

Genetically engineered Sertoli cells are able to survive allogeneic transplantation

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

Vaccination with leukemia cells expressing cell-surface-associated GM-CSF blocks leukemia induction in immunocompetent mice

Contact Info

Product

Resources

About