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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

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Abstract

Background

Clinically effective T-cell responses can be elicited by single peptide vaccination with Wilms' tumor 1 (WT1) epitope 126–134 in patients with acute myeloid leukemia (AML). We recently showed that a predominant T-cell receptor (TCR) β chain was associated with vaccine-induced complete remission in an AML patient (patient 1). In this study, we address the question of whether this predominant clone or the accompanying Vβ11 restriction could be found in other AML patients vaccinated with the same WT1 peptide.

Materials and methods

For assessment of Vβ usage, cytotoxic T lymphocytes (CTLs) from four vaccinated patients were divided into specific and non-specific by epitope-specific enrichment. Vβ families were quantified in both fractions using reverse transcribed quantitative PCR. Vβ11-positive ‘complementary determining region 3’ (CDR3) sequences were amplified from these samples, from bone marrow samples of 17 other vaccination patients, and from peripheral blood of six healthy controls, cloned and sequenced.

Results

We observed a clear bias towards Vβ11 usage of the WT1-specific CTL populations in all four patients. The predominant CDR3β amino acid (AA) sequence of patient 1 was detected in two other patients. CDR3β loops with closely related AA sequences were only found in patient 1. There were no CDR3β AA sequences with side chains of identical chemical properties detected in any patient.

Conclusion

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.

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Acknowledgments

We thank Susanne Wojtke for technical assistance and Natalie Dürkopp for reviewing the final manuscript. AL and DS are supported by a grant from the José Carreras Leukemia Foundation, the Berliner Krebsgesellschaft, and the Stiftung zur Bekämpfung der Leukämie.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Sebastian Ochsenreither, Alberto Fusi, Anne Geikowski, David Stather, Antonia Busse, Anne Letsch & Ulrich Keilholz

  2. Institute for Biometry and Clinical Epidemiology, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Andrea Stroux

  3. Department of Medicine III, Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Ulrich Keilholz

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  1. Sebastian Ochsenreither
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  2. Alberto Fusi
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Correspondence to Ulrich Keilholz.

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Ochsenreither, S., Fusi, A., Geikowski, A. et al. 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. Cancer Immunol Immunother 61, 313–322 (2012). https://doi.org/10.1007/s00262-011-1099-y

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