Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2
<p>Abstract</p> <p>Background</p> <p>The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopa...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2007-09-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/5/1/42 |
| _version_ | 1818347419553759232 |
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| author | Anders Carey Blackwell Kimberly L Marcom Paul Niedzwiecki Donna Osada Takuya Hobeika Amy Morse Michael A Devi Gayathri R Lyerly H Kim Clay Timothy M |
| author_facet | Anders Carey Blackwell Kimberly L Marcom Paul Niedzwiecki Donna Osada Takuya Hobeika Amy Morse Michael A Devi Gayathri R Lyerly H Kim Clay Timothy M |
| author_sort | Anders Carey |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses.</p> <p>Methods</p> <p>Subjects with stage II (≥ 6 +LN), III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3), mature cultured DC (n = 3), or mature Flt3-ligand mobilized peripheral blood DC (n = 1) loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact.</p> <p>Results</p> <p>All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH) reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up.</p> <p>Conclusion</p> <p>Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00005956</p> |
| first_indexed | 2024-12-13T17:33:52Z |
| format | Article |
| id | doaj.art-51bad104cf5143a28e6b4d97421d6c25 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-13T17:33:52Z |
| publishDate | 2007-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-51bad104cf5143a28e6b4d97421d6c252022-12-21T23:36:59ZengBMCJournal of Translational Medicine1479-58762007-09-01514210.1186/1479-5876-5-42Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2Anders CareyBlackwell Kimberly LMarcom PaulNiedzwiecki DonnaOsada TakuyaHobeika AmyMorse Michael ADevi Gayathri RLyerly H KimClay Timothy M<p>Abstract</p> <p>Background</p> <p>The HER2-inhibiting antibody trastuzumab, in combination with chemotherapy, significantly improves survival of women with resected, HER2-overexpressing breast cancers, but is associated with toxicities including a risk of cardiomyopathy. Additionally, the beneficial effect of trastuzumab is expected to decrease once the drug is discontinued. We proposed to address these concerns by using cancer vaccines to stimulate HER2 intracellular domain (ICD)-specific T cell and antibody responses.</p> <p>Methods</p> <p>Subjects with stage II (≥ 6 +LN), III, or stage IV breast cancerwith > 50% HER2 overexpressing tumor cells who were disease-free after surgery and adjuvant therapy were eligible. Vaccines consisted of immature, cultured DC (n = 3), mature cultured DC (n = 3), or mature Flt3-ligand mobilized peripheral blood DC (n = 1) loaded with ICD, or tetanus toxoid, keyhole limpet hemocyanin or CMV peptide as controls, and were administered intradermally/subcutaneously four times at 3 week intervals. ICD-specific T cell and antibody responses were measured. Cardiac function was determined by MUGA or ECHO; long term disease status was obtained from patient contact.</p> <p>Results</p> <p>All seven patients successfully underwent DC generation and five received all 4 immunizations. There were no toxicities greater than grade 1 or ejection fraction decrements below normal. Delayed-type hypersensitivity (DTH) reactions at the injection site occurred in 6/7 patients and HER2 specificity was detected by cytokine flow cytometry or ELISPOT in 5 patients. At more than 5 years of follow-up, 6/7 had detectable anti-ICD antibodies. One patient experienced a pulmonary recurrence at 4 years from their study immunizations. This recurrence was resected and they are without evidence of disease. All patients are alive and disease-free at 4.6–6.7 years of follow-up.</p> <p>Conclusion</p> <p>Although this was a small pilot study, the well-tolerated nature of the vaccines, the lack of cardiac toxicity, significant immunogenicity, and a 100% 4.5-year survival rate suggest that vaccination with HER2 ICD protein-containing DC is appropriate for further study in this population.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00005956</p>http://www.translational-medicine.com/content/5/1/42 |
| spellingShingle | Anders Carey Blackwell Kimberly L Marcom Paul Niedzwiecki Donna Osada Takuya Hobeika Amy Morse Michael A Devi Gayathri R Lyerly H Kim Clay Timothy M Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2 Journal of Translational Medicine |
| title | Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2 |
| title_full | Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2 |
| title_fullStr | Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2 |
| title_full_unstemmed | Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2 |
| title_short | Long term disease-free survival and T cell and antibody responses in women with high-risk Her2+ breast cancer following vaccination against Her2 |
| title_sort | long term disease free survival and t cell and antibody responses in women with high risk her2 breast cancer following vaccination against her2 |
| url | http://www.translational-medicine.com/content/5/1/42 |
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