Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA)

Salgaller, Michael L.; Lodge, Patricia A.; McLean, Joanne G.; Tjoa, B. A.; Loftus, Douglas J.; Ragde, Haakon; Kenny, Gerald M.; Rogers, M.; Boynton, Alton L.; Murphy, Gerald P.

doi:10.1002/(sici)1097-0045(19980501)35:2<144::aid-pros8>3.0.co;2-j

Cited by 99 publications

(38 citation statements)

References 30 publications

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“…23 In addition, immunological monitoring documented enhanced cellular immunity in patients treated with peptide-pulsed DC. 3 However, the majority of treated prostate cancer patients were resistant to DC-based immunotherapies, suggesting that this approach should be further improved. 8 As it has been shown, DC numbers decrease in prostate cancer tissues in comparison to benign prostatic hyperplasia (BPH) tissues 24 and the levels of infiltrating DC further decreases with the increase of anaplastic grade.…”

Section: Discussionmentioning

confidence: 99%

“…1 Furthermore, tumor-induced immunosuppression was also repeatedly documented in prostate cancer patients. 2,3 We have recently demonstrated that human prostate cancer cell lines caused apoptosis of dendritic cells (DC), the key regulatory cells of the immune system responsible for the induction of specific antitumor immune responses. 4 DC are the most powerful professional antigen presenting cells which recognize tumor antigens, process then, and present antigenic peptides to the T-cells in conjunction with MHC class I or II molecules.…”

Section: Introductionmentioning

confidence: 99%

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TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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We have recently shown that human prostate cancer (PCa) cells induced apoptotic death of the most potent antigen-presenting cells, dendritic cells (DC), which are responsible for the induction of specific antitumor immune responses. Here we have evaluated the effect of murine PCa cells RM-1 on the survival of immature and tumor necrosis factor-a (TNF-a)-stimulated mature DC. PCa cells and DC were co-incubated for 24 -48 h and DC apoptosis was assessed by morphologic criteria, Annexin V assay, and TUNEL staining. We have shown that co-incubation of RM-1 cells with DC is accompanied by an increased level of DC apoptosis, which was mediated by decreased expression of anti-apoptotic protein Bcl-2. Stimulation of DC maturation by TNF-a resulted in increased resistance of DC to PCa-induced apoptosis. In TNF-a treated mature DC, but not in immature DC, the expression of Bcl-2 was not blocked after exposure to RM-1-derived factors. Thus, these data suggest that TNF-a-induced maturation of DC increases their resistance to PCa induced apoptosis. This is likely to be due to the stabilizing of the expression of anti-apoptotic protein Bcl-2. The difference in the sensitivity of mature and immature DC to PCa-induced cell death should be considered during the design of DC-based clinical trials for PCa patients. Prostate Cancer and Prostatic Diseases (2001) 4, 221-227.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Pirtskhalaishvili

Shurin

Esche

et al. 2001

Prostate Cancer Prostatic Dis

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“…However, since autoimmune prostatitis is not life threatening, prostate tissue-specific vaccine candidates could also be utilized in prostate cancer patients with existing prostate glands. The development of tissue-specific vaccine candidates for prostate cancer provides a signifi- cant advantage, as few widely expressed prostate tumor antigens have been identified to date [5][6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Identification of naturally processed CD8 T cell epitopes from prostein, a prostate tissue‐specific vaccine candidate

Friedman¹,

Spies²,

Kalos³

2004

Eur J Immunol

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Prostein is a prostate tissue-specific protein that is uniquely and abundantly expressed in normal and cancerous prostate tissues. Due to this expression profile, we examined the immunogenicity of prostein as a potential vaccine candidate for prostate cancer. To determine the presence of CD8 T cells specific for naturally processed prostein-derived epitopes in healthy individuals, we developed and applied an in vitro stimulation protocol. Using this protocol, we identified CD8 T cells specific for prostein in the peripheral blood of a male and a female donor. Prostein-specific CD8 T cell clones specifically recognized prosteinexpressing targets, including prostate tumor cell lines expressing the relevant HLA alleles. CD8 T cell clones isolated from the male donor were significantly less effective in recognizing target cells compared to cells isolated from the female donor and appeared to recognize subdominant epitopes. The identification of a prostein-specific CD8 T cell repertoire supports the development of prostein in vaccination strategies against prostate cancer. Furthermore, the naturally processed peptide epitopes identified provide tools for the development of peptide-based vaccination strategies against prostate cancer and for monitoring of prostein-specific responses in vaccinated patients.

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“…PCa tumors are low in immunogenicity due to the lack of MHC class I molecules in the majority of cases (3). However, tumor-induced immunosuppression was well documented in PCa patients (4,5). It has been recently demonstrated that tumor causes apoptotic death of key immunocompetent cells, including the major APCs, dendritic cells (DC) (6,7).…”

mentioning

confidence: 99%

Transduction of Dendritic Cells with Bcl-xL Increases Their Resistance to Prostate Cancer-Induced Apoptosis and Antitumor Effect in Mice

Pirtskhalaishvili¹,

Shurin²,

Gambotto³

et al. 2000

The Journal of Immunology

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We have shown that prostate cancer (PCa) causes apoptosis of dendritic cells (DC), which might block the development of specific antitumor immune responses. Analysis of murine prostatic carcinoma tissues revealed the significant decrease in intratumoral DC number during tumor progression. We demonstrated that the cytokine-mediated increase in DC survival was accompanied by an elevated expression of the anti-apoptotic protein Bcl-xL. Next, we evaluated the resistance to tumor-induced apoptosis and the antitumor efficiency of genetically engineered DC overexpressing Bcl-xL. DC were transduced with an adenoviral vector encoding the murine Bcl-xL gene and injected intratumorally. Data analysis revealed that treatment of PCa-bearing mice with Bcl-xL-transduced DC resulted in significant inhibition of tumor growth compared with the administration of nontransduced DC. Thus, our data suggest that the protection of DC from PCa-induced apoptosis might significantly increase the efficacy of DC-based therapies in cancer even in the absence of available tumor-specific Ags.

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Report of immune monitoring of prostate cancer patients undergoing T-cell therapy using dendritic cells pulsed with HLA-A2-specific peptides from prostate-specific membrane antigen (PSMA)

Cited by 99 publications

References 30 publications

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

TNF-α protects dendritic cells from prostate cancer-induced apoptosis

Identification of naturally processed CD8 T cell epitopes from prostein, a prostate tissue‐specific vaccine candidate

Transduction of Dendritic Cells with Bcl-xL Increases Their Resistance to Prostate Cancer-Induced Apoptosis and Antitumor Effect in Mice

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