Vaccination of hormone‐refractory prostate cancer patients with peptide cocktail‐loaded dendritic cells: Results of a phase I clinical trial

Fuessel, Susanne; Meye, Axel; Schmitz, Marc; Zastrow, Stefan; Linné, C.; Richter, K.; Lobel, B.; Hakenberg, Oliver W.; Hoelig, Kristina; Rieber, Ernst Peter; Wirth, Manfred P.

doi:10.1002/pros.20404

Cited by 109 publications

(77 citation statements)

References 48 publications

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“…Nevertheless, several ion channel modulators are already in clinical use or currently tested in clinical trials [5,141]. Moreover, ion channels are considered as targets for vaccination against tumour-associated antigens [142]. The extracellular domains of the channels and transporters are accessible for antibodies [143].…”

Section: Ion Channels As Drug Targetsmentioning

confidence: 99%

Ion channels in cancer: future perspectives and clinical potential

Läng

Stournaras

2014

Phil. Trans. R. Soc. B

136

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Ion transport across the cell membrane mediated by channels and carriers participate in the regulation of tumour cell survival, death and motility. Moreover, the altered regulation of channels and carriers is part of neoplastic transformation. Experimental modification of channel and transporter activity impacts tumour cell survival, proliferation, malignant progression, invasive behaviour or therapy resistance of tumour cells. A wide variety of distinct Ca 2+ permeable channels, K + channels, Na + channels and anion channels have been implicated in tumour growth and metastasis. Further experimental information is, however, needed to define the specific role of individual channel isoforms critically important for malignancy. Compelling experimental evidence supports the assumption that the pharmacological inhibition of ion channels or their regulators may be attractive targets to counteract tumour growth, prevent metastasis and overcome therapy resistance of tumour cells. This short review discusses the role of Ca 2+ permeable channels, K + channels, Na + channels and anion channels in tumour growth and metastasis and the therapeutic potential of respective inhibitors.

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Section: Ion Channels As Drug Targetsmentioning

confidence: 99%

Ion channels in cancer: future perspectives and clinical potential

Läng

Stournaras

2014

Phil. Trans. R. Soc. B

136

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“…While the main aim of this phase I trial was the induction of specifi c immune response, a biochemical response could also be observed in 6 out of 14 patients, who showed a signifi cant decrease in PSA serum levels (30% or more from the baseline) compared to previous studies using antigenpresenting cells loaded with diff erent antigen sources (such as peptides, proteins or mRNA), which reported reductions in serum PSA levels only sporadically (Tjoa et al, 1999;Mu et al, 2005;Fuessel et al, 2006). However, due to the heterogeneity of our patient cohort, we could not discount that the diff erent stages and PSA levels before the treatment may have infl uenced the observed biochemical responses.…”

Section: The Chilean Vaccine Against Prostate Cancer: Re-sultsmentioning

confidence: 85%

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer

et al. 2013

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Here we summarize 10 years of eff ort in the development of a biomedical innovation with global projections. This innovation consists of a novel method for the production of therapeutic dendritic-like cells called Tumor Antigen Presenting Cells (TAPCells ® ). TAPCells-based immunotherapy was tested in more than 120 stage III and IV melanoma patients and 20 castration-resistant prostate cancer patients in a series of phase I and I/II clinical trials. TAPCells vaccines induced T cell-mediated memory immune responses that correlated with increased survival in melanoma patients and prolonged prostate-specifi c antigen doubling time in prostate cancer patients. Importantly, more than 60% of tested patients showed a Delayed Type Hypersensitivity (DTH) reaction against the lysates, indicating the development of anti-tumor immunological memory that correlates with clinical benefi ts. The in vitro analysis of the lysate mix showed that it contains damage-associated molecular patterns such as HMBG-1 protein which are capable to improve, through Toll-like receptor-4, maturation and antigen cross-presentation of the dendritic cells (DC). In fact, a Toll-like receptor-4 polymorphism correlates with patient clinical outcomes. Moreover, Concholepas concholepas hemocyanin (CCH) used as adjuvant proved to be safe and capable of enhancing the immunological response. Furthermore, we observed that DC vaccination resulted in a three-fold increase of T helper-1 lymphocytes releasing IFN-γ and a two-fold increase of T helper-17 lymphocytes capable of producing IL-17 in DTH+ with respect to DTH-patients. Important steps have been accomplished for TAPCells technology transfer, including patenting, packaging and technology assessment. Altogether, our results indicate that TAPCells vaccines constitute an exceptional Chilean national innovation of international value.

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“…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. 172 It is suggested that vaccination with a cocktail of peptides derived from different antigens might be superior treatment modality due to the genetic and biologic heterogeneity of PC. 172 In a different vaccination approach targeting PAP (Dendreon Corp, Seattle, WA, USA, formerly Activated Cell Therapy), in association with the Mayo Clinic, developed the DC therapy APC8015 (Provenge) for the potential treatment of hormone-refractory PC.…”

Section: Dc-based Pc Vaccinesmentioning

confidence: 99%

“…172 It is suggested that vaccination with a cocktail of peptides derived from different antigens might be superior treatment modality due to the genetic and biologic heterogeneity of PC. 172 In a different vaccination approach targeting PAP (Dendreon Corp, Seattle, WA, USA, formerly Activated Cell Therapy), in association with the Mayo Clinic, developed the DC therapy APC8015 (Provenge) for the potential treatment of hormone-refractory PC. In this approach, DC were isolated from patients with hormonerefractory metastatic PC, loaded ex vivo with a recombinant fusion protein consisting of PAP linked to GM-CSF (designated PA2024), and reinfused into patients.…”

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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Vaccination of hormone‐refractory prostate cancer patients with peptide cocktail‐loaded dendritic cells: Results of a phase I clinical trial

Cited by 109 publications

References 48 publications

Ion channels in cancer: future perspectives and clinical potential

Ion channels in cancer: future perspectives and clinical potential

TAPCells, the Chilean dendritic cell vaccine against melanoma and prostate cancer

Immunology and immunotherapy approaches for prostate cancer

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