Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells

Yong Liu; Maurizio Chiriva-Internati; Changxuan You; Rongcheng Luo; Hong You; C. Krishna Prasad; Fabio Grizzi; Everardo Cobos; V. Suzanne Klimberg; Helen Kay; Jawahar L. Mehta; Paul L. Hermonat

doi:10.1038/sj.cgt.7700785

Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells

Yong Liu, Maurizio Chiriva-Internati, Changxuan You, Rongcheng Luo, Hong You, C. Krishna Prasad, Fabio Grizzi, Everardo Cobos, V. Suzanne Klimberg, Helen Kay, Jawahar L. Mehta, Paul L. Hermonat

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Antigen-targeted immunotherapy is an emerging treatment for breast cancer. However, useful breast cancer antigens are only found in a subset of cancer patients. BA46, also known as lactadherin, is a membrane-associated glycoprotein that is expressed in most breast cancer cells but not in general hematopoietic cell populations. Moreover, it is much more difficult to generate CTLs against self-antigens. We wished to determine if the use of recombinant adeno-associated virus (rAAV) type 2 vectors for gene-loading of dendritic cells (DCs) could generate rapid, effective cytotoxic T lymphocytes (CTLS) against BA46. We were able to demonstrate that AAV/BA46/Neo-loading of DCs resulted in: (1) BA46 expression in DCs, (2) chromosomal integration of the AAV/BA46/Neo vector within DCs, (3) strong, rapid BA46-specific, MHC class I-restricted CTLs in only 1 week, (4) T-cell populations with significant interferon-γ (IFN-γ) expression but low IL-4 expression, (5) high CD80 and CD86 expression in DCs, and (6) high CD8:CD4 and CD8:CD56 T cell ratios. These data suggest that rAAV-loading of DCs may be useful for immunotherapeutic protocols against self-antigens in addition to viral antigens and that the BA46 antigen is potentially appropriate for cell-mediated immunotherapeutic protocols addressing ductal breast cancer.

Original language	English (US)
Pages (from-to)	304-312
Number of pages	9
Journal	Cancer gene therapy
Volume	12
Issue number	3
DOIs	https://doi.org/10.1038/sj.cgt.7700785
State	Published - Mar 2005
Externally published	Yes

Keywords

Adeno-associated virus
BA46
Breast cancer
Cytotoxic T lymphocyte
Dendritic cell
Immunology

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cancer Research

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10.1038/sj.cgt.7700785

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Liu, Y., Chiriva-Internati, M., You, C., Luo, R., You, H., Prasad, C. K., Grizzi, F., Cobos, E., Klimberg, V. S., Kay, H., Mehta, J. L., & Hermonat, P. L. (2005). Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells. Cancer gene therapy, 12(3), 304-312. https://doi.org/10.1038/sj.cgt.7700785

Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells. / Liu, Yong; Chiriva-Internati, Maurizio; You, Changxuan et al.
In: Cancer gene therapy, Vol. 12, No. 3, 03.2005, p. 304-312.

Research output: Contribution to journal › Article › peer-review

Liu, Y, Chiriva-Internati, M, You, C, Luo, R, You, H, Prasad, CK, Grizzi, F, Cobos, E, Klimberg, VS, Kay, H, Mehta, JL & Hermonat, PL 2005, 'Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells', Cancer gene therapy, vol. 12, no. 3, pp. 304-312. https://doi.org/10.1038/sj.cgt.7700785

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title = "Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells",

abstract = "Antigen-targeted immunotherapy is an emerging treatment for breast cancer. However, useful breast cancer antigens are only found in a subset of cancer patients. BA46, also known as lactadherin, is a membrane-associated glycoprotein that is expressed in most breast cancer cells but not in general hematopoietic cell populations. Moreover, it is much more difficult to generate CTLs against self-antigens. We wished to determine if the use of recombinant adeno-associated virus (rAAV) type 2 vectors for gene-loading of dendritic cells (DCs) could generate rapid, effective cytotoxic T lymphocytes (CTLS) against BA46. We were able to demonstrate that AAV/BA46/Neo-loading of DCs resulted in: (1) BA46 expression in DCs, (2) chromosomal integration of the AAV/BA46/Neo vector within DCs, (3) strong, rapid BA46-specific, MHC class I-restricted CTLs in only 1 week, (4) T-cell populations with significant interferon-γ (IFN-γ) expression but low IL-4 expression, (5) high CD80 and CD86 expression in DCs, and (6) high CD8:CD4 and CD8:CD56 T cell ratios. These data suggest that rAAV-loading of DCs may be useful for immunotherapeutic protocols against self-antigens in addition to viral antigens and that the BA46 antigen is potentially appropriate for cell-mediated immunotherapeutic protocols addressing ductal breast cancer.",

keywords = "Adeno-associated virus, BA46, Breast cancer, Cytotoxic T lymphocyte, Dendritic cell, Immunology",

author = "Yong Liu and Maurizio Chiriva-Internati and Changxuan You and Rongcheng Luo and Hong You and Prasad, {C. Krishna} and Fabio Grizzi and Everardo Cobos and Klimberg, {V. Suzanne} and Helen Kay and Mehta, {Jawahar L.} and Hermonat, {Paul L.}",

note = "Funding Information: Drs Yong Liu and Maurizio Chiriva-Internati contributed equally to this work. This work was funded by a grant from the Arkansas Foundation for Breast Cancer Research.",

year = "2005",

month = mar,

doi = "10.1038/sj.cgt.7700785",

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AU - Liu, Yong

AU - Chiriva-Internati, Maurizio

AU - You, Changxuan

AU - Luo, Rongcheng

AU - You, Hong

AU - Prasad, C. Krishna

AU - Grizzi, Fabio

AU - Cobos, Everardo

AU - Klimberg, V. Suzanne

AU - Kay, Helen

AU - Mehta, Jawahar L.

AU - Hermonat, Paul L.

N1 - Funding Information: Drs Yong Liu and Maurizio Chiriva-Internati contributed equally to this work. This work was funded by a grant from the Arkansas Foundation for Breast Cancer Research.

PY - 2005/3

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N2 - Antigen-targeted immunotherapy is an emerging treatment for breast cancer. However, useful breast cancer antigens are only found in a subset of cancer patients. BA46, also known as lactadherin, is a membrane-associated glycoprotein that is expressed in most breast cancer cells but not in general hematopoietic cell populations. Moreover, it is much more difficult to generate CTLs against self-antigens. We wished to determine if the use of recombinant adeno-associated virus (rAAV) type 2 vectors for gene-loading of dendritic cells (DCs) could generate rapid, effective cytotoxic T lymphocytes (CTLS) against BA46. We were able to demonstrate that AAV/BA46/Neo-loading of DCs resulted in: (1) BA46 expression in DCs, (2) chromosomal integration of the AAV/BA46/Neo vector within DCs, (3) strong, rapid BA46-specific, MHC class I-restricted CTLs in only 1 week, (4) T-cell populations with significant interferon-γ (IFN-γ) expression but low IL-4 expression, (5) high CD80 and CD86 expression in DCs, and (6) high CD8:CD4 and CD8:CD56 T cell ratios. These data suggest that rAAV-loading of DCs may be useful for immunotherapeutic protocols against self-antigens in addition to viral antigens and that the BA46 antigen is potentially appropriate for cell-mediated immunotherapeutic protocols addressing ductal breast cancer.

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KW - Cytotoxic T lymphocyte

KW - Dendritic cell

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Use and specificity of breast cancer antigen/milk protein BA46 for generating anti-self-cytotoxic T lymphocytes by recombinant adeno-associated virus-based gene loading of dendritic cells

Abstract

Keywords

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