Tumor-peptide-pulsed dendritic cells isolated from spleen or cultured in vitro from bone marrow precursors can provide protection against tumor challenge

Hermans, Ian F.; Daish, Angela; Moroni-Rawson, Pisana; Ronchese, Franca

doi:10.1007/s002620050392

Cited by 46 publications

(36 citation statements)

References 22 publications

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“…Genetically modified or peptide-pulsed DC can generate immunity to established tumors or tumor challenge (29,30). In this study, we report the effect of combined intratumor injection of DISC/mGM-CSF and syngeneic bone marrow-derived DC on the growth of s.c. CT26 tumors.…”

Section: Discussionmentioning

confidence: 99%

Tumor Regression Induced by Intratumor Therapy with a Disabled Infectious Single Cycle (DISC) Herpes Simplex Virus (HSV) Vector, DISC/HSV/Murine Granulocyte-Macrophage Colony-Stimulating Factor, Correlates with Antigen-Specific Adaptive Immunity

Ali

Lynam

McLean³

et al. 2002

The Journal of Immunology

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Direct intratumor injection of a disabled infectious single cycle HSV-2 virus encoding the murine GM-CSF gene (DISC/mGM-CSF) into established murine colon carcinoma CT26 tumors induced a significant delay in tumor growth and complete tumor regression in up to 70% of animals. Pre-existing immunity to HSV did not reduce the therapeutic efficacy of DISC/mGM-CSF, and, when administered in combination with syngeneic dendritic cells, further decreased tumor growth and increased the incidence of complete tumor regression. Direct intratumor injection of DISC/mGM-CSF also inhibited the growth of CT26 tumor cells implanted on the contralateral flank or seeded into the lungs following i.v. injection of tumor cells (experimental lung metastasis). Proliferation of splenocytes in response to Con A was impaired in progressor and tumor-bearer, but not regressor, mice. A potent tumor-specific CTL response was generated from splenocytes of all mice with regressing, but not progressing tumors following in vitro peptide stimulation; this response was specific for the gp70 AH-1 peptide SPSYVYHQF and correlated with IFN-γ, but not IL-4 cytokine production. Depletion of CD8+ T cells from regressor splenocytes before in vitro stimulation with the relevant peptide abolished their cytolytic activity, while depletion of CD4+ T cells only partially inhibited CTL generation. Tumor regression induced by DISC/mGM-CSF virus immunotherapy provides a unique model for evaluating the immune mechanism(s) involved in tumor rejection, upon which tumor immunotherapy regimes may be based.

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Section: Discussionmentioning

confidence: 99%

Tumor Regression Induced by Intratumor Therapy with a Disabled Infectious Single Cycle (DISC) Herpes Simplex Virus (HSV) Vector, DISC/HSV/Murine Granulocyte-Macrophage Colony-Stimulating Factor, Correlates with Antigen-Specific Adaptive Immunity

Ali

Lynam

McLean³

et al. 2002

The Journal of Immunology

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“…To this end, CFSE ϩ DC loaded with the MHC class I-binding peptide LCMV 33-41 were administered to mice that had been injected s.c. in the flank 7 days before with 10 5 DC alone or with 10 5 DC loaded with the same LCMV 33-41 peptide. The 7-day interval was chosen because our previous studies have shown that Ag-specific T cell expansion is maximal at this time (22); also, resistance to challenge with LCMV 33-41 -expressing tumors can be demonstrated (17). In addition, "memory" recipients were also used.…”

Section: Clearance Of Ag-loaded DC Is Accelerated In the Presence Of mentioning

confidence: 99%

“…For these studies we used the tumor cell line LL-LCMV, a Lewis lung carcinoma expressing the LCMV 33-41 epitope (17). All mice were preimmunized s.c. in the flank with DC loaded with OVA 257-264 to induce OVA 257-264 -specific CTL responses.…”

Section: Ctl-mediated Clearance Of Tumor Ag-loaded DC From the Lymph mentioning

confidence: 99%

CD8+ T Cell-Dependent Elimination of Dendritic Cells In Vivo Limits the Induction of Antitumor Immunity

Hermans

Ritchie

Yang

et al. 2000

The Journal of Immunology

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211

206

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The fate of dendritic cells (DC) after they have initiated a T cell immune response is still undefined. We have monitored the migration of DC labeled with a fluorescent tracer and injected s.c. into naive mice or into mice with an ongoing immune response. DC not loaded with Ag were detected in the draining lymph node in excess of 7 days after injection with maximum numbers detectable ∼40 h after transfer. In contrast, DC that had been loaded with an MHC class I-binding peptide disappeared from the lymph node with kinetics that parallel the known kinetics of activation of CD8+ T cells to effector function. In the presence of high numbers of specific CTL precursors, as in TCR transgenic mice, DC numbers were significantly decreased by 72 h after injection. The rate of DC disappearance was extremely rapid and efficient in recently immunized mice and was slower in “memory” mice in which memory CD8+ cells needed to reacquire effector function before mediating DC elimination. We also show that CTL-mediated clearance of Ag-loaded DC has a notable effect on immune responses in vivo. Ag-specific CD8+ T cells failed to divide in response to Ag presented on a DC if the DC were targets of a pre-existing CTL response. The induction of antitumor immunity by tumor Ag-loaded DC was also impaired. Therefore, CTL-mediated clearance of Ag-loaded DC may serve as a negative feedback mechanism to limit the activity of DC within the lymph node.

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“…B16.F10 melanoma expressing gp33 (B16.gp33, [31]) and Lewis lung carcinoma expressing gp33 (LL-LCMV, [32]) were maintained in cIMDM containing 0.5 mg/mL Geneticin s (GIBCO, Auckland, New Zealand).…”

Section: Tumor Cell Linesmentioning

confidence: 99%

“…Mice were challenged with 2 Â 10 5 B16.gp33 cells or 1 Â 10 5 LL-LCMV cells in the left flank, and examined every 2-3 days to monitor tumor growth as described [32].…”

Section: Tumor Protectionmentioning

confidence: 99%

Effector CD8⁺ T cells activated in vitro confer immediate and long‐term tumor protection in vivo

Perret

Ronchese

2008

Eur J Immunol

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We studied the ability of CD8 1 T cells activated in vitro to mediate tumor protection after transfer into adoptive hosts. TCR transgenic CD8 1 T cells were activated in culture with DC and specific peptide antigen, and briefly expanded in IL-2 containing medium. Cultured cells acquired a CD44 hi CD62L lo phenotype, and following in vivo transfer they preferentially homed to non-lymphoid tissues and spleen. In vivo, their numbers declined between day 0 and day 20, and then remained relatively stable from day 20 to day 90. Over time, many of the injected cells re-expressed CD62L, and acquired the ability to localize to secondary lymphoid organs. Transferred T cells underwent low-level proliferation, expressed IL-7Ra and IL-15Rb, were cytotoxic in vivo, and retained the ability to produce IL-2, IFN-c and TNF-a upon ex vivo restimulation. In addition, transferred T cells conferred a high degree of tumor protection, which was greatest immediately after injection, and remained significant even when tumor was given 90 days after T-cell transfer. We conclude that in vitro generated effector T cells can mediate immediate and long-term tumor protection, and develop into long-lived memory T-cell populations in vivo.

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Tumor-peptide-pulsed dendritic cells isolated from spleen or cultured in vitro from bone marrow precursors can provide protection against tumor challenge

Cited by 46 publications

References 22 publications

Tumor Regression Induced by Intratumor Therapy with a Disabled Infectious Single Cycle (DISC) Herpes Simplex Virus (HSV) Vector, DISC/HSV/Murine Granulocyte-Macrophage Colony-Stimulating Factor, Correlates with Antigen-Specific Adaptive Immunity

Tumor Regression Induced by Intratumor Therapy with a Disabled Infectious Single Cycle (DISC) Herpes Simplex Virus (HSV) Vector, DISC/HSV/Murine Granulocyte-Macrophage Colony-Stimulating Factor, Correlates with Antigen-Specific Adaptive Immunity

CD8+ T Cell-Dependent Elimination of Dendritic Cells In Vivo Limits the Induction of Antitumor Immunity

Effector CD8⁺ T cells activated in vitro confer immediate and long‐term tumor protection in vivo

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Tumor-peptide-pulsed dendritic cells isolated from spleen or cultured in vitro from bone marrow precursors can provide protection against tumor challenge

Cited by 46 publications

References 22 publications

Tumor Regression Induced by Intratumor Therapy with a Disabled Infectious Single Cycle (DISC) Herpes Simplex Virus (HSV) Vector, DISC/HSV/Murine Granulocyte-Macrophage Colony-Stimulating Factor, Correlates with Antigen-Specific Adaptive Immunity

Tumor Regression Induced by Intratumor Therapy with a Disabled Infectious Single Cycle (DISC) Herpes Simplex Virus (HSV) Vector, DISC/HSV/Murine Granulocyte-Macrophage Colony-Stimulating Factor, Correlates with Antigen-Specific Adaptive Immunity

CD8+ T Cell-Dependent Elimination of Dendritic Cells In Vivo Limits the Induction of Antitumor Immunity

Effector CD8+ T cells activated in vitro confer immediate and long‐term tumor protection in vivo

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Effector CD8⁺ T cells activated in vitro confer immediate and long‐term tumor protection in vivo