Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

Eertwegh, Alfons J.M. van den; Versluis, Jurjen; Berg, H. Pieter van den; Santegoets, Saskia J.; Moorselaar, R. Jeroen A. van; Sluis, Tim M. van der; Gall, Helen; Harding, Thomas C.; Jooss, Karin; Lowy, Israel; Pinedo, H.M.; Scheper, Rik J.; Stam, Anita G.M.; Blomberg, B. Mary E. von; Gruijl, Tanja D. de; Hege, Kristen; Sacks, Natalie; Gerritsen, Winald R.

doi:10.1016/s1470-2045(12)70007-4

Cited by 336 publications

(217 citation statements)

References 35 publications

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“…The first anecdotal data that anti-CTLA-4 treatment after DC vaccination may indeed enhance DC vaccine-induced T-cell responses was published in 2005 (89), and there is some evidence that anti-CTLA-4 antibodies might be more effective after DC vaccination (90). In addition, two small trials have shown that DC-based immunotherapy in combination with anti-CTLA-4 antibodies seems to be more effective than the use of these agents alone, showing a best overall response rate of 38% in melanoma patients (91,92), as is suggested in results from multiple small trials with other forms of antigen-specific immunotherapy (93,94). Currently, no clinical data on the combination of DC vacciation with anti-PD-1 antibodies are available, but anti-PD-1 antibodies are being investigated in combination with DC vaccination and the first results are expected in 2016 (Table 2).…”

Section: Combination With Immune Checkpoint Inhibitors: the Ideal Commentioning

confidence: 97%

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Bol

Schreibelt

Gerritsen

et al. 2016

Clinical Cancer Research

290

241

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Dendritic cell (DC) vaccination in cancer patients aims to induce or augment an effective antitumor immune response against tumor antigens and was first explored in a clinical trial in the 1990s. More than two decades later, numerous clinical trials have been performed or are ongoing with a wide variety of DC subsets, culture protocols, and treatment regimens. The safety of DC vaccination and its ability to induce antitumor responses have clearly been established; however, although scattered patients with long-term benefit were reported, DC vaccines have not yet fulfilled their promise, perhaps mainly due to the lack of large-scale well-conducted phase II/III trials. To allow meaningful multicenter phase III trials, the production of DC vaccines should be standardized between centers which is now becoming feasible. To improve the efficacy of DC-based immunotherapy, it could be combined with other treatments.

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Section: Combination With Immune Checkpoint Inhibitors: the Ideal Commentioning

confidence: 97%

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Bol

Schreibelt

Gerritsen

et al. 2016

Clinical Cancer Research

290

241

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“…These patients were very sick and did not receive any checkpoint blockade in addition to the prostate GVAX vaccine to overcome tumor-induced immune suppression. 28 , 29 Two patients in cohort C and one patient in cohort B displayed an increase in prostate-specific antigen doubling time (PSA-DT) post-treatment, suggestive of reduced tumor growth. Additional clinical assessment and immune monitoring performed for this trial will be described elsewhere (Curti et al., and Puri et al.…”

Section: Resultsmentioning

confidence: 99%

“…This could be explained due to low activation induction of monocytes/DCs using the LNCaP DRibbles compared to the UbiLT3 DRibbles. Also, in a clinical trial where mCRPC patients received GVAX in combination with ipilimumab 28 no T cell responses in IFN-γ ELIspot were observed after 10-day IVS with LNCaP cells, whereas responses were seen using PC3 cells as stimulators (unpublished data: personal communication with Prof. TD. de Gruijl).…”

Section: Discussionmentioning

confidence: 99%

“…40 In the majority of the clinical trials, the focus is on serum PSA responses, humoral responses as well as T cell activation or CD4-responses. 19 , 28 , 29 , 41-44 No autologous tumors were available from the patients from this trial, making it impossible to test whether the CD8 + T cells recognizing antigens in the UbiLT3 DRibble vaccine could also recognize and kill autologous tumor cells. The lack of primary tumor also prevented the search for patient-specific neo-epitopes and CD8 + T cells recognizing such epitopes.…”

Section: Discussionmentioning

confidence: 99%

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Autophagosome-based strategy to monitor apparent tumor-specific CD8 T cells in patients with prostate cancer

Ven

Hilton

Hu³

et al. 2018

OncoImmunology

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The immune system plays an essential role in eradicating cancer in concert with various treatment modalities. In the absence of autologous tumor material, no standardized method exists to assess T cell responses against the many antigens that may serve as cancer rejection antigens. Thus, development of methods to screen for therapy-induced anti-tumor responses is a high priority that could help tailor therapy. Here we tested whether a tumor-derived antigen source called DRibbles®, which contain a pool of defective ribosomal products (DRiPs), long-lived and short-lived proteins (SLiPs) and danger-associated molecular patterns (DAMPs), can be used to identify tumor-associated antigen (TAA)-specific responses in patients before or after immunotherapy treatment. Protein content, gene expression and non-synonymous – single nucleotide variants (ns-SNVs) present in UbiLT3 DRibbles were compared with prostate adenocarcinomas and the prostate GVAX vaccine cell lines (PC3/LNCaP). UbiLT3 DRibbles were found to share proteins, as well as match tumor sequences for ns-SNVs with prostate adenocarcinomas and with the cell lines PC3 and LNCaP. UbiLT3 DRibbles were used to monitor anti-tumor responses in patients vaccinated with allogeneic prostate GVAX. UbiLT3-DRibble-reactive CD8+ T-cell responses were detected in post-vaccine PBMC of 6/12 patients (range 0.85–22% of CD8+ cells) after 1 week in vitro stimulation (p = 0.007 vs. pre-vaccine). In conclusion, a cancer-derived autophagosome-enriched preparation, packaging over 100 proteins over-expressed in prostate cancer into microvesicles containing DAMPs, could be used to identify CD8+ T cells in peripheral blood from patients after prostate GVAX vaccination and may represent a general method to monitor anti-cancer T cell responses following immunotherapy.

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“…183,185-187 In several instances, vaccination is further combined with standard treatment regimens including conventional chemotherapy, 117,188-191 radiation therapy, 52,192-195 and targeted anticancer agents, 196-199 or with various immunotherapeutic interventions. 200-205 The latter include (1) immune checkpoint blockers such as the anti-PD-1 mAbs pembrolizumab and nivolumab, 206-208 the anti-PD-L1 mAbs durvalumab and atezolizumab, 209-211 and the anti-CTLA4 mAb ipilimumab; 137,186,212-215 (2) immunostimulatory antibodies such as utomilumab, which stimulates TNF receptor superfamily member 9 (TNFRSF9; best known as 4-1BB or CD137) signaling, 28,216-218 or the CD27 agonist varlilumab; 28,216,219,220 and immunomodulatory agents such as lenalidomide. 221-224 In line with preclinical and clinical data demonstrating that multi-epitope vaccines are generally more powerful than their single-epitope counterparts, 117,225 the most common vaccination strategy employed by these studies consists in targeting simultaneously multiple TAAs (20 studies).…”

Section: Ongoing Clinical Trialsmentioning

confidence: 99%

Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

Cited by 336 publications

References 35 publications

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Autophagosome-based strategy to monitor apparent tumor-specific CD8 T cells in patients with prostate cancer

Trial watch: Peptide-based vaccines in anticancer therapy

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