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Cancer Immunology, Immunotherapy

, Volume 57, Issue 2, pp 271–280 | Cite as

Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer

  • Helga Bernhard
  • Julia Neudorfer
  • Kerstin Gebhard
  • Heinke Conrad
  • Christine Hermann
  • Jörg Nährig
  • Falko Fend
  • Wolfgang Weber
  • Dirk H. Busch
  • Christian Peschel
Short Communication

Abstract

The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.

Keywords

Tumor immunity Human Cytotoxic T cells Antigens/peptides/epitopes MHC 

Abbreviations

HER2

Human epidermal growth factor receptor 2

111In

Indium-111

SPECT

Single photon emission computed tomography

MRI

Magnetic resonance tomography

FDG-PET

[18F] Fluorodeoxyglucose positron emission tomography

MNC

Mononuclear cell

Notes

Acknowledgments

We thank the patients for taking part in this clinical trial; Burkhard Schmidt, Evelyn Schulz and Matthias Schiemann for excellent technical assistance; Peter Schmidkonz for expert clinical care; and Wendy Batten for helpful discussion and critical reading of the manuscript. This work was supported by the Research Council of Germany grant SFB 456 (to H.B. and D.H.B.) and the Wilhelm Sander-Stiftung grant 2000.017.3 (to H.B.).

Supplementary material

262_2007_355_MOESM1_ESM.doc (40 kb)
ESM1 (DOC 40.5 kb)

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Helga Bernhard
    • 1
    • 5
    • 6
  • Julia Neudorfer
    • 1
  • Kerstin Gebhard
    • 1
    • 5
  • Heinke Conrad
    • 1
  • Christine Hermann
    • 1
  • Jörg Nährig
    • 2
  • Falko Fend
    • 2
  • Wolfgang Weber
    • 3
  • Dirk H. Busch
    • 4
    • 5
  • Christian Peschel
    • 1
  1. 1.Department of Hematology/OncologyTechnical University of MunichMunichGermany
  2. 2.Department of PathologyTechnical University of MunichMunichGermany
  3. 3.Department of Nuclear MedicineTechnical University of MunichMunichGermany
  4. 4.Department of Microbiology, Immunology and HygieneTechnical University of MunichMunichGermany
  5. 5.Clinical Cooperation Group ‘Antigen-Specific Immunotherapy’GSF, Institute of Health and Environment Neuherberg and Technical University of MunichNeuherbergGermany
  6. 6.3rd Medical DepartmentTechnical University of MunichMunichGermany

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