An HLA-DR–Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2–Specific Immunity in Patients with Cancer

Kalli, Kimberly R.; Krco, Christopher J.; Hartmann, Lynn C.; Goodman, Karin M.; Maurer, Mathew S.; Yu, Chao; Johnson, Elliot M.; Erskine, Courtney L.; Disis, Mary L.; Wettstein, Peter J.; Fikes, John; Beebe, Melanie; Ishioka, Glenn; Knutson, Keith L.

doi:10.1158/0008-5472.can-07-6726

Cited by 16 publications

(27 citation statements)

References 57 publications

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“…All six family members are secreted and expressed in normal ovarian tissue, although previous studies have shown that IGFBP-2 serum levels and expression to be significantly increased in ovarian cancer tissue in comparison with controls [167-170]. We revealed for the first time that IGFBP-2 elicits an in vivo antigen-specific CD4 T cell immunity in patients with ovarian cancer [171]. In that study, T cells from >15% of the patients elicited a response against four HLA-DR-degenerate IGFBP-2 epitopes compared with controls.…”

Section: Targeted Antigens In Ovarian Cancermentioning

confidence: 93%

RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer

Knutson

Karyampudi

Lamichhane

et al. 2014

Cancer Metastasis Rev

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Clinical outcomes, such as recurrence free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies.

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Section: Targeted Antigens In Ovarian Cancermentioning

confidence: 93%

RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer

Knutson

Karyampudi

Lamichhane

et al. 2014

Cancer Metastasis Rev

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“…In that experiment, peripheral blood T cells were stimulated with a pool of HLA-DR epitopes derived from the FRα or IGFBP2. Both of these antigens are highly expressed in a high percentage of patients with ovarian cancer and some patients with ovarian cancer demonstrate natural immunity to these antigens (32, 33). As shown, patients treated with MV-NIS augmented immune responses to both antigens but not to tetanus, which was added as a control for specificity of the immune response.…”

Section: Resultsmentioning

confidence: 99%

“…To detect tumor-specific T-cell immunity, a degenerate panel of peptides derived from either the folate receptor alpha (FRα; FR30, FR56, FR113, and FR238) or insulin-like growth factor binding protein 2 (IGFBP2; IGFBP2.17, IGFBP2.22, IGFBP2.249, and IGFBP2.293), as previously described, was used (32, 33). The plates were read on an AID ELISpot reader (Cell Technology, Inc.; reader software v.3.1.1.).…”

Section: Methodsmentioning

confidence: 99%

Oncolytic Measles Virus Expressing the Sodium Iodide Symporter to Treat Drug-Resistant Ovarian Cancer

et al. 2015

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Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS in patients with taxol- and platinum-resistant ovarian cancer. MV-NIS was given intraperitoneally every 4 weeks for up to 6 cycles. Treatment was well tolerated and associated with promising median overall survival in these patients with heavily pretreated ovarian cancer; no dose-limiting toxicity was observed in 16 patients treated at high-dose levels (108–109 TCID50), and their median overall survival of 26.5 months compared favorably with other contemporary series. MV receptor CD46 and nectin-4 expression was confirmed by immunohistochemistry in patient tumors. Sodium iodide symporter expression in patient tumors after treatment was confirmed in three patients by 123I uptake on SPECT/CTs and was associated with long progression-free survival. Immune monitoring posttreatment showed an increase in effector T cells recognizing the tumor antigens IGFBP2 and FRα, indicating that MV-NIS treatment triggered cellular immunity against the patients' tumor and suggesting that an immune mechanism mediating the observed antitumor effect. Our findings support further clinical evaluation of MV-NIS as an effective immunovirotherapy.

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“…All six family members are secreted and expressed in normal ovarian tissue, although previous studies have shown IGFBP-2 serum levels and expression to be significantly increased in ovarian cancer tissue in comparison with controls [45–48]. We revealed for the first time that IGFBP-2 elicits an in vivo antigen-specific CD4 T-cell immunity in patients with breast and ovarian cancer [49]. In this study, T cells from more than 15% of the patients elicited a response against four HLA-DR-degenerate IGFBP-2 epitopes compared with controls.…”

Section: Antigen Specificity Of the Ovarian Cancer Immune Responsementioning

confidence: 91%

Immunity and Immune Suppression in Human Ovarian Cancer

et al. 2011

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Clinical outcomes in ovarian cancer are heterogeneous, independent of common features such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling issue is the response of the patient’s immune system to her ovarian cancer. Several studies have confirmed a prominent role for the immune system in modifying disease course. This has led to the identification and evaluation of novel immune-modulating therapeutic approaches such as vaccination and antibody therapy. Antitumor immunity, however, is often negated by immune suppression mechanisms present in the tumor microenvironment. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological issues that could influence ovarian cancer outcome, including tumor antigens, endogenous immune responses, immune escape and new and developing immunotherapeutic strategies.

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An HLA-DR–Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2–Specific Immunity in Patients with Cancer

Abstract: Recent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I-based vaccines.

Cited by 16 publications

References 57 publications

RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer

RETRACTED ARTICLE: Targeted immune therapy of ovarian cancer

Oncolytic Measles Virus Expressing the Sodium Iodide Symporter to Treat Drug-Resistant Ovarian Cancer

Immunity and Immune Suppression in Human Ovarian Cancer

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