Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer

Eaton, J.D.; Perry, M.J.A.; Nicholson, S.; Guckian, M.; Russell, N.; Whelan, M.; Kirby, R.S.

doi:10.1046/j.1464-4096.2001.01511.x

Cited by 10 publications

(10 citation statements)

References 10 publications

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“…In the current clinical trial model, new vaccines are usually tested in patients with late- or end-stage disease who have been heavily pretreated and have exhausted other treatment options. However, numerous vaccine studies (the GVAX [40, 41] and PSA vaccine trials [42] in prostate cancer, the idiotype vaccine trials in follicular lymphoma [43], and adjuvant immunotherapy trials in melanoma [44]) have shown that immunotherapy is less effective in patients with heavy disease burden [45], providing a biological rationale for using therapeutic vaccines earlier in the disease process. Greater tumor burden leads to an increase in regulatory T cells (Tregs) [46, 47] and myeloid-derived suppressor cells, as well as increased levels of indoleamine-2,3-dioxygenase and negative regulatory cytokines such as transforming growth factor-β and interleukin-10, all of which can inhibit T-cell activation [48, 49].…”

Section: Patient Selection In Immunotherapy Trialsmentioning

confidence: 99%

Endpoints, patient selection, and biomarkers in the design of clinical trials for cancer vaccines

Bilušić

Gulley

2011

Cancer Immunol Immunother

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Therapeutic cancer vaccines are an emerging and potentially effective treatment modality. Cancer vaccines are usually very well tolerated, with minimal toxicity compared with chemotherapy. Unlike conventional cytotoxic therapies, immunotherapy does not result in immediate tumor shrinkage, but may alter growth rate and thus prolong survival. Multiple randomized controlled trials of various immunotherapeutic agents have shown a delayed separation in Kaplan-Meier survival curves, with no evidence of clinical benefit within the first 6 to 12 months of vaccine treatment. Overall survival benefit is seen in patients with lower disease burden who are not expected to die within those initial 6 to 12 months. The concept of improved overall survival without marked initial tumor reduction represents a significant shift from the current paradigms established by standard cytotoxic therapies. Future clinical studies of therapeutic vaccines should enroll patients with lower tumor burden, more indolent disease, or both, and must seek to identify early markers of clinical benefit that may correlate with survival. Until then, improved overall survival is the only clear, discriminatory endpoint for therapeutic vaccines as monotherapies.

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Section: Patient Selection In Immunotherapy Trialsmentioning

confidence: 99%

Endpoints, patient selection, and biomarkers in the design of clinical trials for cancer vaccines

Bilušić

Gulley

2011

Cancer Immunol Immunother

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“…This highlights the need for careful selection of cell lines used in allogeneic vaccines to match the antigenic profile of the patient. However, as the principle of whole-cell vaccination is based on targeting of unknown epitopes, many such vaccines are composed of a mixture of several cell lines that are hoped to give the best antigenic spread [23][24][25][26].…”

Section: Vaccines Using Unmodified Autologous or Allogeneic Cellsmentioning

confidence: 99%

Overview of Tumor Cell–Based Vaccines

Copier

Dalgleish

2006

International Reviews of Immunology

101

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Whole-cell tumor vaccines have been investigated for more than 20 years for their efficacy in both preclinical models and in clinical trials in humans. There are clear advantages of whole-cell/polyepitope vaccination over those types of immunotherapy that target specific epitopes. Multiple and unknown antigens may be targeted to both the innate and adaptive immune system, and this may be further augmented by genetic modification of the vaccine cells to provide cytokines and costimulation. In this review, we give an overview of the field including the preclinical and clinical advances using unmodified and modified tumor-cell vaccines.

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“…In einer Phase-I Studie wurden 60 Patienten mit einem hormonrefraktären Prostatakarzinom und einem PSA-Wert > 30 ng/ml eingeschlossen und behandelt [26]. Mycobacterium vaccae SRL172 wurde simultan als Adjuvants verabreicht.…”

Section: Onyvax-p (Onyvax Ltd)unclassified

“…Eine statistisch relevante Verlangsamung der PSA-Anstiegsgeschwindigkeit wurde bei 3/13 Patienten beobachtet [30]. Therapiebedingte Nebenwirkungen waren bei allen Patienten von milder Natur (Grad 1 und 2) und äußerten sich als Hautreaktionen (Rötung, Schwellung, Schmerz, Juckreiz) an der Injektionsstelle, gastrointestinale Beschwerden und grippeähnliche Symptome, die nach 1 bis 2 Tagen wieder verschwanden [19,26].…”

Section: Onyvax-p (Onyvax Ltd)unclassified

Vakzinetherapie des Prostatakarzinoms

Doehn¹,

Böhmer²,

Sommerauer³

et al. 2005

Tumordiagn u Ther

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ZusammenfassungDie Vakzinetherapie des Prostatakarzinoms unter Studienbedingungen hat erst in den letzten Jahren an Bedeutung gewonnen. Die verschiedenen Vakzinetechniken sind sehr variabel und werden in erster Linie bei Patienten mit fortgeschrittenem Prostatakarzinom und nach Versagen einer antihormonellen Therapie eingesetzt. In der vorliegenden Übersichtsarbeit werden Vakzinetechniken mit Tumorzellen, mit dendritischen Zellen oder mit Pockenviren analysiert. Für diese Ansätze sind Studien der Phase-III geplant, begonnen oder sogar abgeschlossen. Viele Studien zeigen eine Effektivität im Hinblick auf die Endpunkte einer Immunantwort und/oder biochemischem und/oder klinischem Ansprechen. Kürzlich konnte sogar für eine Vakzine mit autologen dendritischen Zellen gezeigt werden, dass es gegenüber Plazebo zu einer statistisch signifikanten Lebensverlängerung bei Patienten mit einem hormonrefraktären Prostatakarzinom kommt. Das Nebenwirkungsprofil der Vakzinetherapie ist dabei als äußerst günstig zu bezeichnen. Derzeit befinden sich Studien in Planung, die sowohl auf eine Kombination mit anderen Substanzen als auch auf die Behandlung früherer Krankheitsstadien abzielen. SchlüsselwörterProstatakarzinom · Immuntherapie · Vakzine · Tumorzelle · dendritische Zelle · Virus · Antigen · Zytokin · Wachstumsfaktor. AbstractVaccine therapy of prostate cancer has been increasingly studied in trials over the past few years. The different vaccine techniques are quite variable and are predominantly used in patients with advanced hormone-refractory prostate cancer. In this review, vaccine techniques using tumor cells, dendritic cells or poxvirus are analyzed. For theses approaches phase-III trials are being planned, have been initiated or are already completed. Many trials demonstrate the efficacy with regard to endpoints such as stimulation of the immune system and/or biochemical response and/or clinical response. Recently, one vaccine approach using autologous dendritic cells demonstrated a statistically significant prolongation of overall survival compared to placebo in patients with hormone-refractory prostate cancer. Side effects of vaccination are generally mild. At present, there are trials are being planned or are already ongoing that combine vaccine with other treatment strategies or enroll patients with earlier disease stages.

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Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer

Cited by 10 publications

References 10 publications

Endpoints, patient selection, and biomarkers in the design of clinical trials for cancer vaccines

Endpoints, patient selection, and biomarkers in the design of clinical trials for cancer vaccines

Overview of Tumor Cell–Based Vaccines

Vakzinetherapie des Prostatakarzinoms

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