Expansion of HER2/neu-specific T cells ex vivo following immunization with a HER2/neu peptide-based vaccine

Keith L Knutson, M. L. Disis

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The identification and characterization of tumor antigens has facilitated the development of immune-based cancer prophylaxis and therapy. Cancer vaccines, like viral vaccines, may be effective in cancer prevention. Adoptive T-cell therapy, in contrast, may be more efficacious for the eradication of existing malignancies. Our group is examining the feasibility of antigen-specific adoptive T-cell therapy for the treatment of established cancer in the HER2/neu model. Transgenic mice overexpressing rat neu in mammary tissue develop malignancy, histologically similar to human HER2/neu-overexpressing breast cancer. These mice can be effectively immunized against a challenge with neu-positive tumor cells. Adoptive transfer of neu-specific T cells into tumor-bearing mice eradicates malignancy. Effective T-cell therapy relies on optimization of the ex vivo expansion of antigen-specific T cells. Two important elements of ex vivo antigen-specific T-cell growth that have been identified are (1) the preexisting levels of antigen-specific T cells and (2) the cytokine milieu used during ex vivo expansion of the T cells. Phase I clinical trials of HER2/neu-based peptide vaccination in human cancer patients have demonstrated that increased levels of HER2/neu-specific T cells can be elicited after active immunization. Initiating cultures with greater numbers of antigen-specific T cells facilitates expansion. In addition, cytokines, such as interleukin-12, when added during ex vivo culturing along with interleukin-2 can selectively expand antigen-specific T cells. Interleukin-12 also enhances antigen-specific functional measurements such as interferon-gamma and tumor necrosis factor-alpha release. Refinements in ex vivo expansion techniques may greatly improve the feasibility of tumor-antigen T-cell-based therapy for the treatment of advanced-stage HER2/neu-overexpressing breast malignancy.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalClinical Breast Cancer
Volume2
Issue number1
StatePublished - 2001
Externally publishedYes

Fingerprint

Subunit Vaccines
Immunization
T-Lymphocytes
Antigens
Neoplasms
Cell- and Tissue-Based Therapy
Neoplasm Antigens
Interleukin-12
Vaccination
Breast
Viral Vaccines
Cytokines
Clinical Trials, Phase I
Cancer Vaccines
Adoptive Transfer
Transgenic Mice
Interferon-gamma
Interleukin-2
Therapeutics
Tumor Necrosis Factor-alpha

Keywords

  • Adoptive T-cell therapy
  • Breast cancer
  • Cancer vaccines
  • Cytokines
  • HER2/neu

ASJC Scopus subject areas

  • Cancer Research

Cite this

Expansion of HER2/neu-specific T cells ex vivo following immunization with a HER2/neu peptide-based vaccine. / Knutson, Keith L; Disis, M. L.

In: Clinical Breast Cancer, Vol. 2, No. 1, 2001, p. 73-79.

Research output: Contribution to journalArticle

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