Abstract
Recent studies of immune responses to pathogens have identified pathogen-associated molecular patterns (PAMPs) recognized by the innate immune system through specialized receptors called toll-like receptors (TLRs). Signaling through these receptors initiates robust immune responses. By exploiting TLR signaling pathways, immunity to tumor-associated antigens may be generated. Many tumor-associated antigens are involved in the regulation of tumor phenotype or carcinogenesis. Immune targeting of these antigens may either alter the tumor phenotype, yielding a more treatable tumor, or eradicate early tumor stem cells preventing tumor formation. The oncoprotein HER-2/neu, which is over-expressed in a significant number of pre-malignant breast lesions of ductal carcinoma in situ (DCIS), may provide such a target. Immune responses directed against HER-2/neu may eliminate the disease, make tumors more amenable to anti-estrogen therapy, or prevent escape of hormone-resistant tumor phenotypes. Effective breast cancer prevention in preclinical studies utilizing HER-2/neu transgenic murine models has stimulated interest in, and optimism regarding, protective breast cancer vaccines in humans. Induction of anti-HER-2/neu T cell (CD4+ and CD8+) and B cell responses has been demonstrated in an ongoing clinical study targeting HER-2/neu using a TLR agonist stimulated dendritic cell (DC) vaccine. Moreover, these vaccinations lead to reductions in both HER-2/ neu expression and extent of DCIS. HER-2/neu expression and aromatase activity have recently been linked through the intermediary cyclooxygenase 2 (COX2). This convergence between growth factor and hormone mediated pathways reinforces the notion that a significant number of breast cancers may be prevented through effective immune targeting of HER-2/neu. As progress is made in the development of vaccines for breast cancer prevention, the contributions of immune-mediated effector and inhibitory mechanisms to the pathogenesis of HER-2/neu over-expressing breast cancers will need to be better understood.
| Original language | English |
|---|---|
| Pages (from-to) | 97-107 |
| Number of pages | 11 |
| Journal | Current Cancer Therapy Reviews |
| Volume | 3 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2007 May 1 |
| Externally published | Yes |
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Keywords
- Ductal carcinoma in situ
- EGFR family
- Regulatory T Cells
- Trastuzumab
- Tumor Antigen
ASJC Scopus subject areas
- Molecular Medicine
- Oncology
- Cancer Research
Cite this
Working towards the development of vaccines for the treatment and prevention of early breast cancer. / Roses, Robert E.; Xu, Min; Xu, Shuwen; Koldovsky, Ursula; Son, Gil Soo; Koski, Gary K.; Czerniecki, Brian J.
In: Current Cancer Therapy Reviews, Vol. 3, No. 2, 01.05.2007, p. 97-107.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Working towards the development of vaccines for the treatment and prevention of early breast cancer
AU - Roses, Robert E.
AU - Xu, Min
AU - Xu, Shuwen
AU - Koldovsky, Ursula
AU - Son, Gil Soo
AU - Koski, Gary K.
AU - Czerniecki, Brian J.
PY - 2007/5/1
Y1 - 2007/5/1
N2 - Recent studies of immune responses to pathogens have identified pathogen-associated molecular patterns (PAMPs) recognized by the innate immune system through specialized receptors called toll-like receptors (TLRs). Signaling through these receptors initiates robust immune responses. By exploiting TLR signaling pathways, immunity to tumor-associated antigens may be generated. Many tumor-associated antigens are involved in the regulation of tumor phenotype or carcinogenesis. Immune targeting of these antigens may either alter the tumor phenotype, yielding a more treatable tumor, or eradicate early tumor stem cells preventing tumor formation. The oncoprotein HER-2/neu, which is over-expressed in a significant number of pre-malignant breast lesions of ductal carcinoma in situ (DCIS), may provide such a target. Immune responses directed against HER-2/neu may eliminate the disease, make tumors more amenable to anti-estrogen therapy, or prevent escape of hormone-resistant tumor phenotypes. Effective breast cancer prevention in preclinical studies utilizing HER-2/neu transgenic murine models has stimulated interest in, and optimism regarding, protective breast cancer vaccines in humans. Induction of anti-HER-2/neu T cell (CD4+ and CD8+) and B cell responses has been demonstrated in an ongoing clinical study targeting HER-2/neu using a TLR agonist stimulated dendritic cell (DC) vaccine. Moreover, these vaccinations lead to reductions in both HER-2/ neu expression and extent of DCIS. HER-2/neu expression and aromatase activity have recently been linked through the intermediary cyclooxygenase 2 (COX2). This convergence between growth factor and hormone mediated pathways reinforces the notion that a significant number of breast cancers may be prevented through effective immune targeting of HER-2/neu. As progress is made in the development of vaccines for breast cancer prevention, the contributions of immune-mediated effector and inhibitory mechanisms to the pathogenesis of HER-2/neu over-expressing breast cancers will need to be better understood.
AB - Recent studies of immune responses to pathogens have identified pathogen-associated molecular patterns (PAMPs) recognized by the innate immune system through specialized receptors called toll-like receptors (TLRs). Signaling through these receptors initiates robust immune responses. By exploiting TLR signaling pathways, immunity to tumor-associated antigens may be generated. Many tumor-associated antigens are involved in the regulation of tumor phenotype or carcinogenesis. Immune targeting of these antigens may either alter the tumor phenotype, yielding a more treatable tumor, or eradicate early tumor stem cells preventing tumor formation. The oncoprotein HER-2/neu, which is over-expressed in a significant number of pre-malignant breast lesions of ductal carcinoma in situ (DCIS), may provide such a target. Immune responses directed against HER-2/neu may eliminate the disease, make tumors more amenable to anti-estrogen therapy, or prevent escape of hormone-resistant tumor phenotypes. Effective breast cancer prevention in preclinical studies utilizing HER-2/neu transgenic murine models has stimulated interest in, and optimism regarding, protective breast cancer vaccines in humans. Induction of anti-HER-2/neu T cell (CD4+ and CD8+) and B cell responses has been demonstrated in an ongoing clinical study targeting HER-2/neu using a TLR agonist stimulated dendritic cell (DC) vaccine. Moreover, these vaccinations lead to reductions in both HER-2/ neu expression and extent of DCIS. HER-2/neu expression and aromatase activity have recently been linked through the intermediary cyclooxygenase 2 (COX2). This convergence between growth factor and hormone mediated pathways reinforces the notion that a significant number of breast cancers may be prevented through effective immune targeting of HER-2/neu. As progress is made in the development of vaccines for breast cancer prevention, the contributions of immune-mediated effector and inhibitory mechanisms to the pathogenesis of HER-2/neu over-expressing breast cancers will need to be better understood.
KW - Ductal carcinoma in situ
KW - EGFR family
KW - Regulatory T Cells
KW - Trastuzumab
KW - Tumor Antigen
UR - http://www.scopus.com/inward/record.url?scp=34249337754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249337754&partnerID=8YFLogxK
U2 - 10.2174/157339407780618461
DO - 10.2174/157339407780618461
M3 - Review article
VL - 3
SP - 97
EP - 107
JO - Current Cancer Therapy Reviews
JF - Current Cancer Therapy Reviews
SN - 1573-3947
IS - 2
ER -