Wilms' tumor protein 1 (WT1) peptide vaccination in AML patients: predominant TCR CDR3β sequence associated with remission in one patient is detectable in other vaccinated patients

Ochsenreither, Sebastian; Fusi, Alberto; Geikowski, Anne; Stather, David R.; Busse, Antonia; Stroux, Andrea; Letsch, Anne; Keilholz, Ulrich

doi:10.1007/s00262-011-1099-y

Cited by 18 publications

(13 citation statements)

References 45 publications

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“…In considering other vaccine approaches, in particular DC vaccines, it is noteworthy that Wilms tumor-1 (WT-1) peptide vaccination or vaccination with DCs electroporated with WT1 mRNA in patients with acute myelogenous leukemia (AML) has led to occasional leukemia regression (40,41) or conversion from partial to complete remission following vaccination (42). Therapeutic vaccination with ex vivo-prepared tumor antigenloaded DCs, particularly in patients with metastatic melanoma, has been practiced by numerous groups, mainly with monocytederived, in vitro-cultured DCs.…”

Section: Clinical Cancer Vaccines Against Nonviral Antigensmentioning

confidence: 99%

Therapeutic cancer vaccines

Melief

Hall

Arens

et al. 2015

Journal of Clinical Investigation

707

409

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Conflict of interest: Cornelis J.M. Melief is fully employed as Chief Scientific Officer of ISA Pharmaceuticals and has stock appreciation rights in the company. Cornelis Melief and Sjoerd H. van der Burg are co-inventors on numerous patents and patent applications in the area of synthetic long peptide vaccines. Clinical trials conducted by Melief and van der Burg with synthetic long peptides have been funded by the Dutch Cancer Society and by ISA Pharmaceuticals.

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Section: Clinical Cancer Vaccines Against Nonviral Antigensmentioning

confidence: 99%

Therapeutic cancer vaccines

Melief

Hall

Arens

et al. 2015

Journal of Clinical Investigation

707

409

View full text Add to dashboard Cite

show abstract

“…Studies from Japanese groups clearly demonstrated biased usage of TCR-Vβ gene families in WT1 peptide vaccinated patients [26,27]; the group in Germany observed the WT1 vaccination-induced expansion of a preexisting low abundant TCR clone, which became a specific predominant clone after WT1 peptide vaccination [28]. The bias towards Vβ11 usage of the WT1-specific CTL populations was confirmed in all four patients following a single peptide vaccination [29]. In addition, the identification of a WT1-specific TCR sequence could provide the basis for adoptive transfer of ex vivo expanded WT1-specific TCR engineered CTLs [30].…”

Section: Characterization Of the Wt1 Specific Cd8+ T Cell Repertoirementioning

confidence: 79%

Novel Immunotherapy to Eliminate Minimal Residual Disease in AML Patients

Liu

Kline²

2013

J Hematol Thrombo Diseases

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Even with the most sophisticated chemotherapy regimens, the majority of patients with acute myeloid leukemia will eventually experience a relapse and die from their disease. New treatments are needed to prevent relapse of disease in these patients. Immunotherapy using the host immune system to combat leukemia represents an exciting and potentially efficacious addition to standard chemotherapy for AML. Immune-base treatments may be particularly effective when administered at a time when patients are in clinical remission with normal blood counts; nevertheless, these patients often have minimal residual disease which eventually results in disease relapse. Successful vaccinationbased immunotherapy targeting leukemia-specific antigens will likely require the administration of powerful immune adjutants and removal of negative immune regulatory pathways in order to achieve maximal efficacy. This review article will focus on the rationales underlying our ongoing clinical trial to test the efficacy of WT1 peptide based immunotherapy using TLR3 agonist as adjuvant in combination of the depletion of T regulatory cells with anti-CD25 antibody in patients with hematologic malignancies.

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“…Clearance of residual leukemia through vaccination against WT-1 showcased this antigen as a target cancer vaccination in general [80]. Further, monitoring individual patients by using markers of residual disease could revolutionize this area of investigation by providing fairly rapid proof of principle in small-sized trials [81].…”

Section: Cancer Vaccines In Minimal Residual Disease To Clear Residuamentioning

confidence: 99%

Repositioning therapeutic cancer vaccines in the dawning era of potent immune interventions

Bot

Marincola

Smith³

2013

Expert Review of Vaccines

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Based on lessons learned with various immune interventions, this review aims to provide a constructive framework for repositioning therapeutic cancer vaccination. Intensive research throughout the past decade has identified key hurdles interfering with the efficacy of cancer vaccines. The vaccination concept still holds promise if positioned appropriately in minimal residual disease and select early disease stage cancer indications. However, in advanced cancer, it must be integrated with complementary immune interventions to ensure reconstruction of a functional immune repertoire and simultaneous blockade of immune inhibiting mechanisms. Vaccination could render complex and integrative immune interventions simpler, safer and more effective. The near future will witness an explosion of activities in the cancer immunotherapy arena, witnessing a rational repositioning of vaccines rather than their extinction.

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Wilms' tumor protein 1 (WT1) peptide vaccination in AML patients: predominant TCR CDR3β sequence associated with remission in one patient is detectable in other vaccinated patients

Abstract: We provide the first data addressing TCR Vβ chain usage in WT1-specific T-cell populations after HLA A*0201-restricted single peptide vaccination. We demonstrate both shared Vβ restriction and the sharing of a TCR β transcript with proven clinical impact in one patient.

Cited by 18 publications

References 45 publications

Therapeutic cancer vaccines

Therapeutic cancer vaccines

Novel Immunotherapy to Eliminate Minimal Residual Disease in AML Patients

Repositioning therapeutic cancer vaccines in the dawning era of potent immune interventions

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