A Phase II Study of Human Epidermal Growth Factor Receptor 2 (HER-2) Directed Dendritic Cell (DC1) Vaccine Plus Weekly Paclitaxel, Trastuzumab and Pertuzumab in Patients With HER-2 Positive Breast Cancer

The purpose of the study is to find out if an investigational drug called Dendritic Cell (DC1) vaccine added to standard neoadjuvant (given before main treatment) therapy can help people with HER2 (human epidermal growth factor receptor 2) positive breast cancer.

开始日期2021-10-28

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

NCT03630809

/ Terminated临床2期IIT

Immune Response Surveillance and Potential Booster Vaccines for Patients Who Have Received HER2-pulsed DC1 Vaccine

The purpose of this study is to learn more about how to treat patients with a diagnosis of diagnosis of Human Epidermal Growth Factor Receptor 2/neu (HER-2/neu) positive breast cancer in the past, who were previously treated with HER-2/neu-directed dendritic cells (DC) vaccines.
There is evidence that the use of anti-HER2 dendritic cell (DC) study vaccines could improve response to breast cancer therapy and be an important step in the prevention of recurrence.
This study will use a Dendritic Cell Type 1 (DC1) vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. Dendritic cells are immune cells that can tell the participant's immune system to fight infection. This study vaccine will be made from the participant's blood cells collected from a procedure called leukapheresis.

开始日期2019-01-10

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

NCT02063724

/ Completed临床1期IIT

Pilot Phase I HER-2 Pulsed DC Vaccine to Prevent Recurrence for Patients With HER-2 Driven High Risk Invasive Breast Cancer

The purpose of this study is to determine the safety and immunogenicity of HER-2 pulsed DC1 vaccine in high risk HER-2 high and intermediate expression breast cancers. Participants will have HER-2 driven IBC at least Stage IIIA with N2 following chemotherapy with/without trastuzumab or recurrence exclusive of new primary tumor but rendered NED. Mammogram, laboratory studies, CT, and leukapheresis will be performed, in addition to vaccine administration.

开始日期2014-10-01

申办/合作机构

H. Lee Moffitt Cancer Center & Research Institute, Inc.

[+1]

100 项与 HER-2 pulsed DC1(H. Lee Moffitt Cancer Center and Research Institute) 相关的临床结果

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100 项与 HER-2 pulsed DC1(H. Lee Moffitt Cancer Center and Research Institute) 相关的转化医学

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100 项与 HER-2 pulsed DC1(H. Lee Moffitt Cancer Center and Research Institute) 相关的专利（医药）

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项与 HER-2 pulsed DC1(H. Lee Moffitt Cancer Center and Research Institute) 相关的文献（医药）

2013-10-01·Annals of Surgical Oncology2区 · 医学

Response to HER-2 Pulsed DC1 Vaccines is Predicted by Both HER-2 and Estrogen Receptor Expression in DCIS

2区 · 医学

Article

作者: Brian J Czerniecki ; Robert Roses ; Carla Fisher ; Julia Tchou ; Megan Fracol ; Elizabeth Fitzpatrick ; Rosemarie Mick ; Harvey Nisenbaum ; Shuwen Xu ; Kevin Fox ; Paul Zhang

BACKGROUNDPatients with estrogen-independent (ER(neg)) human epidermal growth factor receptor-2 (HER-2)-positive ductal carcinoma in situ (DCIS) treated with lumpectomy alone or lumpectomy and radiation are at increased risk of developing subsequent breast cancer events.METHODSThirty-eight patients with HER-2 expressing DCIS received a HER-2 pulsed autologous dendritic cell (DC1) vaccine administered over 4-6 weeks before surgical resection. HER-2 and estrogen receptor (ER) expression were determined by immunohistochemistry. In 35 patients, CD4(pos) T-cell sensitization to HER-2 peptides was identified by ELISPOT. In 19 patients, CD8(pos) T-cell responses were identified by ELISA. Clinical and immune responses postvaccination were compared between intermediate-expressing HER-2 (2+) and high-expressing HER-2 (3+) patients, as well as ER(neg) and estrogen-dependent (ER(pos)) patients.RESULTSThere was no significant difference in immune response after HER-2 vaccination in patients with HER-2 (2+) and (3+) tumors or ER(neg) and ER(pos) tumors. Complete tumor regression rates were similar in patients with HER-2 (2+) and (3+) DCIS. Overall, clinical response rates were similar in patients with ER(neg) and ER(pos) DCIS, but complete tumor regression was significantly more common in patients with ER(neg) DCIS.CONCLUSIONSDespite equivalent immune responses after vaccination in patients with HER-2 (2+), HER-2 (3+), ER(neg) and ER(pos) DCIS, HER-2 pulsed DC1 induces more complete responses in patients with ER(neg) DCIS. These data provide a rationale for developing vaccinations to reduce recurrence in patients with ER(neg) DCIS for whom there are currently limited adjuvant options.

Frontiers in Immunology2区 · 医学

Sequential Anti-PD1 Therapy Following Dendritic Cell Vaccination Improves Survival in a HER2 Mammary Carcinoma Model and Identifies a Critical Role for CD4 T Cells in Mediating the Response

2区 · 医学

ArticleOA

作者: Zhang, Hongtao ; Jia, Yongsheng ; Ramamoorthi, Ganesan ; Czerniecki, Brian J ; Wiener, Doris ; Lam, Lian ; Awshah, Sabrina ; Basu, Amrita ; Snyder, Colin ; Costa, Ricardo L B ; Greene, Mark I ; Beyer, Amber P ; Kodumudi, Krithika N

Patients with metastatic HER2 breast cancer (MBC) often become resistant to HER 2 targeted therapy and have recurrence of disease. The Panacea trial suggested that HER2 MBC patients were more likely to respond to checkpoint therapy if TIL were present or if tumor expressed PD-L1. We assessed whether type I polarized dendritic cells (DC1) could improve checkpoint therapy in a preclinical model of HER2⁺ breast cancer. TUBO bearing mice were vaccinated with either MHC class I or class II HER2 peptide pulsed DC1 (class I or class II HER2-DC1) concurrently or sequentially with administration of anti-PD-1 or anti-PDL1. Infiltration of tumors by immune cells, induction of anti-HER2 immunity and response to therapy was evaluated. Class I or class II HER2-DC1 vaccinated mice generated anti-HER2 CD8 or CD4+ T cell immune responses and demonstrated delayed tumor growth. Combining both MHC class I and II HER2-pulsed DC1 did not further result in inhibition of tumor growth or enhanced survival compared to individual administration. Interestingly class II HER2-DC1 led to both increased CD4 and CD8 T cells in the tumor microenvironment while class I peptides typically resulted in only increased CD8 T cells. Anti-PD-1 but not anti-PD-L1 administered sequentially with class I or class II HER2-DC1 vaccine could improve the efficacy of HER2-DC1 vaccine as measured by tumor growth, survival, infiltration of tumors by T cells and increase in systemic anti-HER2 immune responses. Depletion of CD4+ T cells abrogated the anti-tumor efficacy of combination therapy with class II HER2-DC1 and anti-PD-1, suggesting that tumor regression was CD4 dependent. Since class II HER2-DC1 was as effective as class I, we combined class II HER2-DC1 vaccine with anti-rat neu antibodies and anti-PD-1 therapy. Combination therapy demonstrated further delay in tumor growth, and enhanced survival compared to control mice. In summary, Class II HER2-DC1 drives both a CD4 and CD8 T cell tumor infiltration that leads to increased survival, and in combination with anti-HER2 therapy and checkpoint blockade can improve survival in preclinical models of HER2 positive breast cancer and warrants exploration in patients with HER2 MBC.

Breast Cancer Research1区 · 医学

Anti-HER2 CD4+ T-helper type 1 response is a novel immune correlate to pathologic response following neoadjuvant therapy in HER2-positive breast cancer

1区 · 医学

ArticleOA

作者: Xu, Shuwen ; Lewis, David A ; Roses, Robert E ; Fitzpatrick, Elizabeth ; Berk, Erik ; Fisher, Carla ; Rosemblit, Cinthia ; Lowenfeld, Lea ; DeMichele, Angela ; Czerniecki, Brian J ; Datta, Jashodeep ; Zhang, Paul J ; Goodman, Noah

AbstractIntroductionA progressive loss of circulating anti-human epidermal growth factor receptor-2/neu (HER2) CD4+ T-helper type 1 (Th1) immune responses is observed in HER2pos-invasive breast cancer (IBC) patients relative to healthy controls. Pathologic complete response (pCR) following neoadjuvant trastuzumab and chemotherapy (T + C) is associated with decreased recurrence and improved prognosis. We examined differences in anti-HER2 Th1 responses between pCR and non-pCR patients to identify modifiable immune correlates to pathologic response following neoadjuvant T + C.MethodsAnti-HER2 Th1 responses in 87 HER2pos-IBC patients were examined using peripheral blood mononuclear cells pulsed with 6 HER2-derived class II peptides via IFN-γ ELISPOT. Th1 response metrics were anti-HER2 responsivity, repertoire (number of reactive peptides), and cumulative response across 6 peptides (spot-forming cells [SFC]/106 cells). Anti-HER2 Th1 responses of non-pCR patients (n = 4) receiving adjuvant HER2-pulsed type 1-polarized dendritic cell (DC1) vaccination were analyzed pre- and post-immunization.ResultsDepressed anti-HER2 Th1 responses observed in treatment-naïve HER2pos-IBC patients (n = 22) did not improve globally in T + C-treated HER2pos-IBC patients (n = 65). Compared with adjuvant T + C receipt, neoadjuvant T + C — utilized in 61.5 % — was associated with higher anti-HER2 Th1 repertoire (p = 0.048). While pCR (n = 16) and non-pCR (n = 24) patients did not differ substantially in demographic/clinical characteristics, pCR patients demonstrated dramatically higher anti-HER2 Th1 responsivity (94 % vs. 33 %, p = 0.0002), repertoire (3.3 vs. 0.3 peptides, p < 0.0001), and cumulative response (148.2 vs. 22.4 SFC/106, p < 0.0001) versus non-pCR patients. After controlling for potential confounders, anti-HER2 Th1 responsivity remained independently associated with pathologic response (odds ratio 8.82, p = 0.016). This IFN-γ+ immune disparity was mediated by anti-HER2 CD4+T-bet+IFN-γ+ (i.e., Th1) — not CD4+GATA-3+IFN-γ+ (i.e., Th2) — phenotypes, and not attributable to non-pCR patients’ immune incompetence, host-level T-cell anergy, or increased immunosuppressive populations. In recruited non-pCR patients, anti-HER2 Th1 repertoire (3.7 vs. 0.5, p = 0.014) and cumulative response (192.3 vs. 33.9 SFC/106, p = 0.014) improved significantly following HER2-pulsed DC1 vaccination.ConclusionsAnti-HER2 CD4+ Th1 response is a novel immune correlate to pathologic response following neoadjuvant T + C. In non-pCR patients, depressed Th1 responses are not immunologically “fixed” and can be restored with HER2-directed Th1 immune interventions. In such high-risk patients, combining HER2-targeted therapies with strategies to boost anti-HER2 Th1 immunity may improve outcomes and mitigate recurrence.

100 项与 HER-2 pulsed DC1(H. Lee Moffitt Cancer Center and Research Institute) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
HER2阳性乳腺癌	临床2期	美国	H. Lee Moffitt Cancer Center & Research Institute, Inc.	2019-01-10
浸润性乳腺癌	临床1期	美国	H. Lee Moffitt Cancer Center & Research Institute, Inc.	2014-04-08
男性乳腺肿瘤	临床前	美国	H. Lee Moffitt Cancer Center & Research Institute, Inc.	2019-01-10
HER2阳性转移性乳腺癌	临床前	美国	H. Lee Moffitt Cancer Center & Research Institute, Inc.	2019-01-10
非浸润性导管内癌	临床前	美国	H. Lee Moffitt Cancer Center & Research Institute, Inc.	2014-06-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02063724 (Adjuvant, CTgov)	临床1期	浸润性乳腺癌	15	HER-2 pulsed Dendritic Cell Vaccine	製鏇憲積獵觸鏇齋衊艱(憲鏇簾衊艱鏇憲齋衊觸) = 醖膚網顧簾積膚簾鬱淵鑰鑰觸積選觸艱蓋遞淵 (鑰鑰憲夢獵廠鹹獵繭糧, 醖範窪齋製顧餘顧選顧 ~ 獵觸築構遞構簾選壓簾) 更多	-	2019-02-15