A Phase I Trial of the Safety and Immunogenicity of a DNA Plasmid Based Vaccine Encoding the Amino Acids 1-163 of Insulin-Like Growth Factor Binding Protein-2 (IGFBP-2) in Patients With Advanced Ovarian Cancer

This phase I trial is studying the side effects of vaccine therapy in treating patients with stage III-IV or recurrent ovarian cancer. Vaccines made from deoxyribonucleic acid (DNA) may help the body build an effective immune response to kill tumor cells.

开始日期2012-03-06

申办/合作机构

University of Washington

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100 项与 IGFBP-2 DNA质粒疫苗(Fred Hutchinson Cancer Research Center) 相关的临床结果

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100 项与 IGFBP-2 DNA质粒疫苗(Fred Hutchinson Cancer Research Center) 相关的转化医学

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100 项与 IGFBP-2 DNA质粒疫苗(Fred Hutchinson Cancer Research Center) 相关的专利（医药）

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项与 IGFBP-2 DNA质粒疫苗(Fred Hutchinson Cancer Research Center) 相关的文献（医药）

2021-12-01·Clinical Cancer Research1区 · 医学

Immunization with a Plasmid DNA Vaccine Encoding the N-Terminus of Insulin-like Growth Factor Binding Protein-2 in Advanced Ovarian Cancer Leads to High-level Type I Immune Responses

1区 · 医学

Article

作者: Childs, Jennifer S. ; Higgins, Doreen M. ; Liao, John B. ; Dang, Yushe ; Disis, Mary L. ; Coveler, Andrew L. ; Cecil, Denise L. ; Yang, Yi ; Kask, Angela

AbstractPurpose:Cancer vaccines targeting nonmutated proteins elicit limited type I T-cell responses and can generate regulatory and type II T cells. Class II epitopes that selectively elicit type I or type II cytokines can be identified in nonmutated cancer-associated proteins. In mice, a T-helper I (Th1) selective insulin-like growth factor binding protein-2 (IGFBP-2) N-terminus vaccine generated high levels of IFNγ secreting T cells, no regulatory T cells, and significant antitumor activity. We conducted a phase I trial of T-helper 1 selective IGFBP-2 vaccination in patients with advanced ovarian cancer.Patients and Methods:Twenty-five patients were enrolled. The IGFBP-2 N-terminus plasmid-based vaccine was administered monthly for 3 months. Toxicity was graded by NCI criteria and antigen-specific T cells measured by IFNγ/IL10 ELISPOT. T-cell diversity and phenotype were assessed.Results:The vaccine was well tolerated, with 99% of adverse events graded 1 or 2, and generated high levels of IGFBP-2 IFNγ secreting T cells in 50% of patients. Both Tbet+ CD4 (P = 0.04) and CD8 (P = 0.007) T cells were significantly increased in immunized patients. There was no increase in GATA3+ CD4 or CD8, IGFBP-2 IL10 secreting T cells, or regulatory T cells. A significant increase in T-cell clonality occurred in immunized patients (P = 0.03, pre- vs. post-vaccine) and studies showed the majority of patients developed epitope spreading within IGFBP-2 and/or to other antigens. Vaccine nonresponders were more likely to have preexistent IGFBP-2 specific immunity and demonstrated defects in CD4 T cells, upregulation of PD-1, and downregulation of genes associated with T-cell activation, after immunization.Conclusions:IGFBP-2 N-terminus Th1 selective vaccination safely induces type I T cells without evidence of regulatory responses.

2017-07-01·Small2区 · 材料科学

Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy

2区 · 材料科学

Article

作者: Huang, Yongzhuo ; Hu, Ying ; Tao, Jin ; Yang, Yunxu ; Xu, Beihua ; Xu, Jiaojiao

This work aims at developing an immunotherapeutic strategy to deliver a cancer DNA vaccine targeting dendritic cells (DCs), to trigger their maturation and antitumor function, and reduce immune escape using a polymeric nanocomplex of paclitaxel (PTX)-encapsulated sulfobutylether-β-cyclodextrin (SBE)/mannosylated N,N,N-trimethylchitosan (mTMC)/DNA. To enhance DC-targeting and revoke immunosuppression is the major challenge for eliciting effective antitumor immunity. This codelivery system is characterized by using low-dose PTX as an adjuvant that is included inside SBE, and the PTX/SBE further serves as an anionic crosslinker to self-assemble with the cationic mTMC/DNA polyplexes. This system is used in combination with a microneedle for transcutaneous vaccination. Once penetrating into the epidermis, the mannosylated nanocomplexes would preferentially deliver the pTRP-2 DNA vaccine inside the DCs. Phenotypic maturation is demonstrated by the increased expression of costimulatory molecules of CD80 and CD86, and the elevated secretion of IL-12p70. The mixed leucocyte reactions reveal that the PTX/SBE-mTMC/DNA nanocomplexes enhance the proliferation of CD4+ and CD8+ T cells, and inhibit the generation of immune-suppressive FoxP3+ T cells. The system shows high antitumor efficacy in vivo. The PTX/SBE-mTMC/DNA nanocomplexes for DC-targeted codelivery of DNA vaccine and adjuvant PTX yield synergistic effects on the DC maturation and its presenting functions, thus increasing immune stimulation and reducing immune escape.

2014-05-15·Cancer Research1区 · 医学

Elimination of IL-10–Inducing T-Helper Epitopes from an IGFBP-2 Vaccine Ensures Potent Antitumor Activity

1区 · 医学

Article

作者: Higgins, Doreen ; Childs, Jennifer ; Park, Kyong Hwa ; Gad, Ekram ; Disis, Mary L. ; Rastetter, Lauren ; Cecil, Denise L. ; Holt, Gregory E.

AbstractImmunization against self-tumor antigens can induce T-regulatory cells, which inhibit proliferation of type I CD4+ T-helper (TH1) and CD8+ cytotoxic T cells. Type I T cells are required for potent antitumor immunity. We questioned whether immunosuppressive epitopes could be identified and deleted from a cancer vaccine targeting insulin-like growth factor–binding protein (IGFBP-2) and enhance vaccine efficacy. Screening breast cancer patient lymphocytes with IFN-γ and interleukin (IL)-10 ELISPOT, we found epitopes in the N-terminus of IGFBP-2 that elicited predominantly TH1 whereas the C-terminus stimulated TH2 and mixed TH1/TH2 responses. Epitope-specific TH2 demonstrated a higher functional avidity for antigen than epitopes, which induced IFN-γ (P = 0.014). We immunized TgMMTV-neu mice with DNA constructs encoding IGFBP-2 N-and C-termini. T cell lines expanded from the C-terminus vaccinated animals secreted significantly more type II cytokines than those vaccinated with the N-terminus and could not control tumor growth when infused into tumor-bearing animals. In contrast, N-terminus epitope–specific T cells secreted TH1 cytokines and significantly inhibited tumor growth, as compared with naïve T cells, when adoptively transferred (P = 0.005). To determine whether removal of TH2-inducing epitopes had any effect on the vaccinated antitumor response, we immunized mice with the N-terminus, C-terminus, and a mix of equivalent concentrations of both vaccines. The N-terminus vaccine significantly inhibited tumor growth (P < 0.001) as compared with the C-terminus vaccine, which had no antitumor effect. Mixing the C-terminus with the N-terminus vaccine abrogated the antitumor response of the N-terminus vaccine alone. The clinical efficacy of cancer vaccines targeting self-tumor antigens may be greatly improved by identification and removal of immunosuppressive epitopes. Cancer Res; 74(10); 2710–8. ©2014 AACR.

100 项与 IGFBP-2 DNA质粒疫苗(Fred Hutchinson Cancer Research Center) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
卵巢癌	临床2期	-	Fred Hutchinson Cancer Research Center	-
卵巢癌	临床2期	-	University of Washington Bothell	-

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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


NCT01322802 (ASCO2016) 人工标引	临床1期	卵巢癌	25	IGFBP-2 DNA vaccine	(餘獵鑰築積獵範簾觸餘) = Fatigue (12%) and injection site reactions (12%) 選鹽艱範鏇遞製鹹願網 (願廠膚壓鏇鏇繭艱膚鏇 )	积极	2016-06-06