Potent Antitumor Effects of Cd154 Transduced Tumor Cells in Experimental Bladder Cancer

Loskog, Angelica; Björkland, Anna; Brown, Michael P.; Korsgren, Olle; Malmström, Per‐Uno; Tötterman, Thomas H.

doi:10.1016/s0022-5347(05)65928-9

Cited by 38 publications

(29 citation statements)

References 24 publications

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“…This particular vector was successfully used in animal studies aiming to develop an immunogene therapy for bladder cancer. 15 The present results indicate that adenoviruses are promising tools for transferring genes into human bladder cancer cells.…”

Section: Introductionmentioning

confidence: 56%

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Human urinary bladder carcinomas express adenovirus attachment and internalization receptors

et al. 2002

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Section: Introductionmentioning

confidence: 56%

“…15 As a negative control, the Ad-dl70-3 'empty' control vector was used (a kind gift from Dr Frank Graham, McMaster University, Hamilton, Ontario).…”

Section: Adenoviral Vectorsmentioning

confidence: 99%

Human urinary bladder carcinomas express adenovirus attachment and internalization receptors

et al. 2002

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“…Whereas CD154 gene therapy was successfully applied in some animal models of solid tumors including bladder cancer, 16,17 the immunological mechanisms of this therapy remain poorly defined. It has been shown that triggering of CD40 on DCs induces expression of costimulatory signals ( CD80, CD86 ) and adhesion molecules (CD54 ) and leads to efficient cross -priming of CTLs.…”

Section: Discussionmentioning

confidence: 99%

“…To further assess the role of cytotoxic lymphocytes we performed cytotoxicity assays with splenocytes from mice vaccinated with MB49 expressing CD154. Based on previous studies, 17 mice were injected four times in weekly intervals with MB49 expressing CD154 to obtain full protection against a subsequent challenge with parental MB49. Splenocytes from vaccinated mice that rejected a challenge with parental tumor and splenocytes from naïve control mice were isolated, and purified CD8 cells were restimulated with irradiated parental MB49.…”

Section: Cd154 -Expressing Tumor Cells Efficiently Activate Autologoumentioning

confidence: 99%

In vitro activation of cancer patient–derived dendritic cells by tumor cells genetically modified to express CD154

et al. 2002

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Purpose: Triggering of CD40 on antigen-presenting cells via its ligand CD154 is an important event in the initial phase of an immune response against cancer cells. In this study, we investigated the effects of adenoviral CD154 immunomodulatory gene therapy on the activation of human dendritic cells (DCs) in a well-defined in vitro system. Experimental design: Human bladder cancer cell lines and tumor cells from patients with renal cell carcinoma (RCC) were transduced with Ad-CD154 vectors or control vectors. Activation of human in vitro generated DCs after coculture with transduced tumor cells was analyzed. Therapeutic efficacy and cytotoxic Tlymphocyte (CTL) activity were assessed in a subcutaneous (s.c.) murine bladder cancer model. Results: Human bladder cancer cell lines expressing CD154 showed a decreased growth rate, increased apoptosis, and modulated expression of molecules important for recognition by cytotoxic lymphocytes. Further, CD154-expressing allogeneic bladder tumor cell lines and autologous tumor cells from patients with renal cell cancer induced maturation of DCs and stimulated IFN-g production from lymphocytes cocultured with mature DCs. In vivo studies showed that CD154 gene therapy was highly effective in wild-type mice but only minimally effective in nude mice. Consequently, strong tumor-specific CTL activity was detected in mice vaccinated with tumor cells expressing CD154. Conclusions: Using tumor cell lines as well as patient-derived material, we could show that tumor cells expressing CD154 efficiently induce maturation and activation of DCs as well as activation of lymphocytes. Our murine in vivo studies demonstrate that lymphocytes contribute to the observed antitumor effect in a s.c. bladder tumor model. These studies should stimulate CD154 gene therapy approaches for the treatment of urologic malignancies.

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“…For example, we have shown that adenoviruses expressing CD40L in the tumor enhance Th1 immunity with infiltration of T-cells at the same time reducing Tregs and MDSCs and promoting M2 to M1 switch. [54][55][56] In human bladder cancer patients, an adenovirus expressing CD40L induced large T-cell infiltrates in the bladder wall. 57 …”

Section: Conditioning Of Patients Receiving Car T-cell Therapymentioning

confidence: 99%

CAR T-Cell Therapy: The Role of Physical Barriers and Immunosuppression in Lymphoma

2015

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Potent Antitumor Effects of Cd154 Transduced Tumor Cells in Experimental Bladder Cancer

Abstract: Our experimental results suggest that the potent antitumor effects of CD154 gene transduction should be considered for immunostimulatory gene therapy for bladder cancer.

Cited by 38 publications

References 24 publications

Human urinary bladder carcinomas express adenovirus attachment and internalization receptors

Human urinary bladder carcinomas express adenovirus attachment and internalization receptors

In vitro activation of cancer patient–derived dendritic cells by tumor cells genetically modified to express CD154

CAR T-Cell Therapy: The Role of Physical Barriers and Immunosuppression in Lymphoma

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