Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma

Waeckerle-Men, Ying; Allmen, Edith Uetz-von; Fopp, M; Moos, Roger von; Böhme, Christel; Schmid, Hans‐Peter; Ackermann, Daniel; Cerny, Thomas; Ludewig, Burkhard; Groettrup, Marcus; Gillessen, Silke

doi:10.1007/s00262-006-0157-3

Cited by 100 publications

(74 citation statements)

References 39 publications

(48 reference statements)

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“…Recently, PSCA was also found to be expressed in prostate cancer metastases (40) and prostate-unrelated carcinomas such as renal clear cell carcinoma (41), pancreatic adenocarcinoma (42), and glioblastoma (43). PSCA has been successfully used as target molecule for various immunotherapeutic approaches (37,38,(44)(45)(46). In this article we show that the DAP12-based CAR led to ZAP-70 phosphorylation upon cross-linking with its Ag and therefore efficiently reprogrammed the cytotoxicity of YTS-NK cells toward otherwise resistant PSCA-positive tumor cells in vitro and in vivo.…”

mentioning

confidence: 75%

DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy

Töpfer

Cartellieri

Michen

et al. 2015

The Journal of Immunology

190

162

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NK cells are emerging as new effectors for immunotherapy of cancer. In particular, the genetic engraftment of chimeric Ag receptors (CARs) in NK cells is a promising strategy to redirect NK cells to otherwise NK cell–resistant tumor cells. On the basis of DNAX-activation protein 12 (DAP12), a signaling adaptor molecule involved in signal transduction of activating NK cell receptors, we generated a new type of CAR targeting the prostate stem cell Ag (PSCA). We demonstrate in this article that this CAR, designated anti–PSCA-DAP12, consisting of DAP12 fused to the anti-PSCA single-chain Ab fragment scFv(AM1) confers improved cytotoxicity to the NK cell line YTS against PSCA-positive tumor cells when compared with a CAR containing the CD3ζ signaling chain. Further analyses revealed phosphorylation of the DAP12-associated ZAP-70 kinase and IFN-γ release of CAR-engineered cells after contact with PSCA-positive target cells. YTS cells modified with DAP12 alone or with a CAR bearing a phosphorylation-defective ITAM were not activated. Notably, infused YTS cells armed with anti–PSCA-DAP12 caused delayed tumor xenograft growth and resulted in complete tumor eradication in a significant fraction of treated mice. The feasibility of the DAP12-based CAR was further tested in human primary NK cells and confers specific cytotoxicity against KIR/HLA-matched PSCA-positive tumor cells, which was further enhanced by KIR-HLA mismatches. We conclude that NK cells engineered with DAP12-based CARs are a promising tool for adoptive tumor immunotherapy.

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mentioning

confidence: 75%

DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy

Töpfer

Cartellieri

Michen

et al. 2015

The Journal of Immunology

190

162

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“…Multi-epitope immunotherapy strategy using DC loaded with antigenic peptides derived from PSCA, PAP, PSMA and PSA was used for treating six HLA-A2 þ patients with hormone-refractory PC. 171 This approach was shown to be feasible and generated cellular antitumour response. In another phase I clinical trial, eight patients with hormone-refractory PC received four vaccinations with DC loaded with a cocktail of HLA-A2-restricted peptides derived from PSA, PSMA, surviving, prostein and transient receptor potential p8.…”

Section: Dc-based Pc Vaccinesmentioning

confidence: 99%

Immunology and immunotherapy approaches for prostate cancer

Elkord

2007

Prostate Cancer Prostatic Dis

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Several mechanisms that impair the immune response to promote tumour progression are reported. These mechanisms aim to reduce the ability of antigen-presenting cells to present antigen and activate naïve T cells to support an active immune response or to create a suppressive environment that induce non-functional tumour-associated antigen-specific T cells. Prostate cancer (PC) alone accounts for 33% of incident cancer cases and about 9% of all cancer-related deaths among men in the USA during 2006. Whereas androgen deprivation has remained the first line of therapy for advanced PC, other therapies are still required due to progression to an androgen-resistant state and eventually loss of control in patients receiving hormonal therapy. Immunotherapy seems to be a promising approach to enhance tumour-specific T-cell responses in different cancers including prostate. More importantly, clinical trials in advanced PC patients have shown that immunotherapy may generate significant clinical responses. Immunology and immunotherapy aspects of PC with focus on prostate-specific antigen will be presented.

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“…However, cultivation and antigen pulse of human DCs in vitro and injection of these cells into patients is a very labor and cost intensive approach which in addition yielded largely disappoint results [41][42][43][44]. The ideal tool for the improvement of DC-based immunotherapies is the usage of PLGA MS as antigen delivery system.…”

Section: Plga Ms Induced Ctls Recognizementioning

confidence: 99%

The STEAP1_262–270 peptide encapsulated into PLGA microspheres elicits strong cytotoxic T cell immunity in HLA‐A*0201 transgenic mice—A new approach to immunotherapy against prostate carcinoma

et al. 2015

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BACKGROUND. PLGA microsphere-based vaccination has been proven to be effective in immunotherapy of syngeneic model tumors in mice. The critical step for the translation to humans is the identification of immunogenic tumor antigens and potent vaccine formulations to overcome immune tolerance. METHODS. HLA-AÃ 0201 transgenic mice were immunized with eight different human prostate cancer peptide antigens co-encapsulated with TLR ligands into PLGA microspheres and analyzed for antigen-specific and functional cytotoxic T lymphocyte responses. RESULTS. Only vaccination with STEAP1 262-270 peptide encapsulated in PLGA MS could effectively crossprime CTLs in vivo. These CTLs recognized STEAP1 262-270 /HLA-A Ã 0201 complexes on human dendritic cells and prostate cancer cell lines and specifically lysed target cells in vivo. Vaccination with PLGA microspheres was much more potent than with incomplete Freund's adjuvant. CONCLUSIONS. Our data suggests that there exist great differences in the immunogenicity of human PCa peptide antigens despite comparable MHC class I binding characteristics. Immunogenic STEAP1 262-270 peptide encapsulated into PLGA microspheres however was able to induce vigorous and functional antigen-specific CTLs and therefore is a promising novel approach for immunotherapy against advanced stage prostate cancer.

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Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma

Abstract: DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.

Cited by 100 publications

References 39 publications

DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy

DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy

Immunology and immunotherapy approaches for prostate cancer

The STEAP1_262–270 peptide encapsulated into PLGA microspheres elicits strong cytotoxic T cell immunity in HLA‐A*0201 transgenic mice—A new approach to immunotherapy against prostate carcinoma

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Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma

Abstract: DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.

Cited by 100 publications

References 39 publications

DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy

DAP12-Based Activating Chimeric Antigen Receptor for NK Cell Tumor Immunotherapy

Immunology and immunotherapy approaches for prostate cancer

The STEAP1262–270 peptide encapsulated into PLGA microspheres elicits strong cytotoxic T cell immunity in HLA‐A*0201 transgenic mice—A new approach to immunotherapy against prostate carcinoma

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The STEAP1_262–270 peptide encapsulated into PLGA microspheres elicits strong cytotoxic T cell immunity in HLA‐A*0201 transgenic mice—A new approach to immunotherapy against prostate carcinoma