Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient

Löffler, Markus; Chandran, P. Anoop; Laske, Karoline; Schroeder, Christopher; Bonzheim, Irina; Walzer, Mathias; Hilke, Franz J.; Trautwein, Nico; Kowalewski, Daniel J.; Schuster, Heiko; Günder, Marc; Yañez, Viviana A. Carcamo; Mohr, Christopher; Sturm, Marc; Nguyen, Huu Phuc; Rieß, Olaf; Bauer, Peter; Nahnsen, Sven; Nadalin, Silvio; Zieker, Derek; Glatzle, Jörg; Thiel, Karolin; Schneiderhan‐Marra, Nicole; Clasen, Stephan; Bösmüller, Hans; Fend, Falko; Kohlbacher, Oliver; Gouttefangeas, Cécile; Stevanović, Stefan; Königsrainer, Alfred; Rammensee, Hans‐Georg

doi:10.1016/j.jhep.2016.06.027

Cited by 75 publications

(61 citation statements)

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“…Similar to ASXL1, KMT2C mutation was also enriched in late-stage or metastatic status of iCCA (28), breast cancer (29), and prostate cancer (30) and was associated to poor prognosis (31). Especially in AYAs with late-stage CCA, greater ASXL1 and KMT2C mutation rates were detected, which might suggest that CCAs in AYA patients is more aggressive.…”

Section: Discussionmentioning

confidence: 86%

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma

et al. 2020

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Section: Discussionmentioning

confidence: 86%

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma

et al. 2020

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“…27,28 However, in clinical oncology only marginal practical approach on clinical daily basis has been implemented in recent years. [29][30][31] Overwhelming experimental and clinical evidence suggests a key role of innate and adaptive immune system in tumor progression. [32][33][34] Forasmuch, novel diagnostic and therapeutic strategies are urgently needed to tailor a personalized immunologic approach in clinical management of underlying oncological disease.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma

et al. 2017

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. Tumor necrosis as well as tumor-associated macrophages (TAMs) in the tumor invasive front (TIF) have been suggested to have a prognostic value in selected solid tumors, inclusive hilar cholangiocarcinoma. However, little is known regarding their influence on tumor progression and prognosis in intrahepatic cholangiocarcinoma (iCC). . We analyzed surgically resected tumor specimens of human iCC (n = 88) for distribution and localization of TAMs, as defined by expression of CD68, formation of necrosis and extent of peritumoral fibrosis. Abundance of TAMs, tumor necrosis and grade of fibrosis were assessed immunohistochemically and histologically and correlated with clinicopathological characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software.. Patients with tumors characterized by low levels of TAMs in TIF or necrosis showed a significantly decreased 1-, 3- and 5-y recurrence-free survival and a significantly decreased overall survival, when compared with patients with tumors showing high levels of TAMs in TIF or no necrosis. Patients with high density of TAMs in TIF showed significantly lower incidence of tumor recurrence, as well ( < 0.05). Absence of tumor necrosis and TAMs in TIF were confirmed as independent prognostic variables in the multivariate survival analysis (all < 0.05). . High levels of TAMs in TIF or absence of histologic tumor necrosis are associated with a significantly improved recurrence-free and overall survival of patients with iCC. These results suggest TAMs and necrosis as valuable prognostic markers in routine histopathologic evaluation, and might indicate more individualized therapeutic strategies.

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“…As expected with any s.c. vaccination using Montanide 16 or when further adding XS15 as an adjuvant 9 , a granuloma developed. It was palpable from day one and grew to a maximum size of approximately 3 x 5 x 1.5 cm by day 12.…”

Section: Clinical Aspects Of the Vaccination Sitementioning

confidence: 99%

Designing a therapeutic SARS-CoV-2 T-cell-inducing vaccine for high-risk patient groups

Rammensee

Stevanović

Gouttefangeas

et al. 2020

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Here, we describe the preliminary results of an experimental vaccination of a self-experimenting healthy volunteer with eight SARS-CoV-2-derived peptides: five predicted to bind to HLA class I molecules (CD8 peptides) and three predicted to bind to HLA-DR molecules (CD4 peptides). The vaccine formulation also included one long and one short CMV-pp65-derived peptide that had previously been administered to the same individual and could thus act as positive controls. It further contained the new adjuvant XS15 and was administered as an emulsion in Montanide as a single subcutaneous (s.c.) injection. Peripheral blood mononuclear cells (PBMCs) isolated from blood drawn on day 36 before vaccination and day 19 after vaccination were assessed using an ex vivo Interferon-γ ELISpot assay. We detected strong vaccine-induced T-cell responses against all four CD4 peptides and against the recall CMV CD8 epitope, but found no immune responses against the five predicted SARS-CoV-2 CD8 peptides. Antibody reactivity against all the SARS-CoV-2 CD4 peptides, as detected using ELISA, was negative or marginal. We interpret these results in terms of the prospects of a therapeutic vaccine to be applied in symptomatic COVID-19 patients. An advantage of this approach is the possibility to assess efficacy or failure within a short time after vaccination.

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Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient

Abstract: Graphical abstract

Cited by 75 publications

References 28 publications

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma

Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma

Designing a therapeutic SARS-CoV-2 T-cell-inducing vaccine for high-risk patient groups

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