Route of administration influences the antitumor effects of bone marrow-derived dendritic cells engineered to produce interleukin-12 in a metastatic mouse prostate cancer model

Sakaguchi, Takashi; Satoh, Takefumi; Ebara, Shin; Mouraviev, Vladimir; Timme, Terry L.; Thompson, Timothy C.

doi:10.1038/sj.cgt.7700709

Cited by 30 publications

(27 citation statements)

References 27 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 Cells were grown as previously described. 18,[20][21][22] The replication-defective adenoviral vector expressing RTVP-1 (AdRTVP-1) and a control adenoviral vector containing the b-galactosidase gene (Adbgal) were prepared as described, 18 and viral concentration was expressed as plaque-forming units. Western blotting with affinity-purified antibody to RTVP-1 was as described.…”

Section: Cells and Adenoviral Vectorsmentioning

confidence: 99%

Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer

et al. 2006

View full text Add to dashboard Cite

We previously identified a novel p53 target gene, RTVP-1, that possesses unique cytotoxic and immunostimulatory activities which make it potentially useful for cancer gene therapy. To test the therapeutic potential of RTVP-1 in a gene-modified tumor cell-based vaccine model, we used an adenoviral vector capable of efficient transduction and expression of RTVP-1 (AdRTVP-1), together with a highly metastatic mouse prostate cancer cell line (178-2 BMA). A vaccine was prepared with 178-2 BMA cells transduced with AdRTVP-1 or a control adenoviral vector expressing b-galactosidase (Adbgal). After irradiation of the cells, syngeneic 129/Sv mice were vaccinated three times at weekly intervals. After 3 weeks, they were challenged with orthotopic 178-2 BMA cells. After 21 days, fewer than 60% of the RTVP-1-cell-vaccinated mice developed tumors compared to 100% of the control mice. The RTVP-1-cell vaccine significantly reduced primary tumor wet weight compared with control Adbgal-cell vaccine (Po0.0001 at 7 and 14 days). Experimental metastasis to lung was also significantly reduced (P ¼ 0.0377), and survival significantly increased (P ¼ 0.0002). In addition, significantly increased NK and CTL activities were demonstrated in the AdRTVP-1-cell-vaccinated mice. These findings indicate that RTVP-1 gene-modified cell-based vaccines may be useful in the prevention of recurrent prostate cancer.

show abstract

Section: Cells and Adenoviral Vectorsmentioning

confidence: 99%

Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer

et al. 2006

View full text Add to dashboard Cite

show abstract

“…The adjuvant administration of IL-12 after immunization with a vaccinia virus expressing the co-stimulatory molecule B7-1 to tumor-bearing mice similarly enhanced animal survival [106]. Other recent approaches include the co-administration of IL-12 along with tumor antigen-pulsed DC [107] and the engineering of tumor cells or antigen-pulsed DC to express IL-12 alone [108,109] or in combination with IL-18 [66] for enhanced anti-tumor immunity. In humans, many studies have combined IL-12 with peptide vaccines for the improved treatment of cancers.…”

Section: Conclusion and Expert Opinionmentioning

confidence: 99%

Immunotherapy of cancer by IL-12-based cytokine combinations

Weiss

Subleski

Wigginton

et al. 2007

Expert Opinion on Biological Therapy

201

121

View full text Add to dashboard Cite

Cancer is a multi-faceted disease comprising complex interactions between neoplastic and normal cells. Over the past decade, there has been considerable progress in defining the molecular, cellular and environmental contributions to the pathophysiology of tumor development. Despite these advances, the conventional treatment of patients still generally involves surgery, radiotherapy and/ or chemotherapy and the clinical outcome for many of these efforts remains unsatisfactory. Recent studies have highlighted the feasibility of using immunotherapeutic approaches that seek to enhance host immune responses to developing tumors. These strategies include immunomodulatory cytokines, with tumor necrosis factor (TNF) alpha, type I or type II Interferons (IFNs), Interleukins (IL)-2, IL-12, IL-15 and IL-18 being among the most potent inducers of anti-tumor activity in a variety of pre-clinical studies. More recently, some exciting new cytokines have been characterized, such as IL-21, IL-23, IL-27, and their immunomodulatory and anti-tumor effects in vitro and in vivo suggest that they may have considerable promise for future immunotherapy protocols. The promise of cytokine therapy does indeed derive from the identification of these novel cytokines, but even more fundamentally, the field is greatly benefiting from the ever-expanding amount of preclinical data that convincingly demonstrate synergistic and/or novel biological effects that may be achieved through the use of several combinations of cytokines with complementary immunestimulating capabilities. One cytokine in particular, IL-12, holds considerable promise by virtue of the fact that it plays a central role in regulating both innate and adaptive immune responses, can by itself induce potent anti-cancer effects, and synergizes with several other cytokines for increased immunoregulatory and anti-tumor activities. This review will discuss the anti-tumor activity of IL-12, with a special emphasis on its ability to synergize with other cytokines for enhancement of immune effector cell populations and regulation of host-tumor cell interactions and the overall tumor microenvironment.

show abstract

“…[18][19][20] The construction and purification of the adenoviral vectors AdIl-12, AdIL-12/ B7 and Adbgal have been described. [16][17][18][19]21 Mice Male 129/Sv mice were used at 12-16 weeks of age.…”

Section: Cells and Adenoviral Vectorsmentioning

confidence: 99%

“…To this end we have shown that antitumor and antimetastatic prostate cancer therapy can also be initiated with AdIL-12-modified macrophage 18 or dendritic cells 19 injected directly into mouse prostate orthotopic tumors. We undertook the present studies to evaluate if the systemic activities generated following orthotopic delivery of AdIL-12 were transferable via immune cells contained in the spleen of treated animals.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model

et al. 2005

View full text Add to dashboard Cite

We developed a preclinical prostate cancer model to study the feasibility of adoptive immunotherapy for residual tumor following neo-adjuvant in situ adenoviral-vector-mediated interleukin 12 (AdIL-12) gene therapy. Splenocytes were obtained from mice with orthotopic 178-2 BMA metastatic mouse prostate cancers treated previously with AdIL-12, or a vector with the IL-12 genes plus the costimulatory gene B7-1 (AdIL-12/B7), or a control gene (Adbgal). The splenocytes were subsequently injected intravenously into syngeneic mice bearing orthotopic 178-2 BMA tumors generated 3 days previously. Significant orthotopic tumor growth suppression was achieved with splenocytes derived from mice whose tumors had been injected with AdIL-12 compared to splenocytes from control Adbgal mice (P ¼ 0.0005) and splenocytes from AdIL-12/B7-treated mice significantly suppressed spontaneous lung metastases compared to splenocytes from control mice (P ¼ 0.0356). Adoptive transfer of splenocytes from either AdIL-12 (P ¼ 0.004) or AdIL-12/B7 (P ¼ 0.009)-treated mice significantly prolonged survival relative to controls. Transfer of NK and tumor-specific CTL activities was detected and depletion of CD4 þ and CD8 þ T cells by in vitro antibody-mediated complement lysis of the splenocytes prior to injection abrogated the effects. Systemic IL-12 administration delivered by intramuscular AdIL-12 injection enhanced the antitumor effects of adoptive splenocyte transfer and boosted the CTL response. Our data provide evidence that this form of adoptive immunotherapy can enhance the effectiveness of neo-adjuvant in situ IL-12 gene therapy in cases of persistent malignancy.

show abstract

Route of administration influences the antitumor effects of bone marrow-derived dendritic cells engineered to produce interleukin-12 in a metastatic mouse prostate cancer model

Cited by 30 publications

References 27 publications

Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer

Adenoviral vector-mediated RTVP-1 gene-modified tumor cell-based vaccine suppresses the development of experimental prostate cancer

Immunotherapy of cancer by IL-12-based cytokine combinations

Therapeutic effects of adoptive splenocyte transfer following in situ AdIL-12 gene therapy in a mouse prostate cancer model

Contact Info

Product

Resources

About