TY - JOUR
T1 - Expansion of HER2/neu-specific T cells ex vivo following immunization with a HER2/neu peptide-based vaccine
AU - Knutson, K. L.
AU - Disis, M. L.
N1 - Funding Information:
This work was supported for Keith L. Knutson by a fellowship from the Department of Defense Breast Cancer Program and for Mary L. Disis by National Cancer Institute grants R01 CA75163 and R01 CA85374, The Cancer Research Treatment Foundation, and the Department of Defense Breast Cancer Program.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Adoptive T-cell therapy
KW - Breast cancer
KW - Cancer vaccines
KW - Cytokines
KW - HER2/neu
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U2 - 10.3816/CBC.2001.n.014
DO - 10.3816/CBC.2001.n.014
M3 - Article
C2 - 11899386
AN - SCOPUS:0035012198
SN - 1526-8209
VL - 2
SP - 73
EP - 79
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - 1
ER -