Polyfunctional T cell responses are a hallmark of HIV‐2 infection

Duvall, Melody G.; Precopio, Melissa; Ambrozak, David A.; Jaye, Assan; McMichael, Andrew J.; Whittle, Hilton; Roederer, Mario; Rowland‐Jones, Sarah; Koup, Richard A.

doi:10.1002/eji.200737768

Cited by 212 publications

(200 citation statements)

References 50 publications

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“…Moreover, this patient did not develop an antibody response to NY-ESO-1. Polyfunctional T cell responses have been shown to correlate with improved control of viral replication in infectious disease studies, suggesting that an effective vaccine should attempt to elicit this type of response (18,27). NY-ESO-1 specific T cell responses induced by CTLA-4 blockade were polyfunctional and were not observed in clinical non-responders, suggesting that NY-ESO-1 antigen-specific polyfunctional T cells induced by CTLA-4 blockade might be potent effectors.…”

Section: Discussionmentioning

confidence: 99%

CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit

Yuan¹,

Gnjatic

Li³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

320

246

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Section: Discussionmentioning

confidence: 99%

CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit

Yuan¹,

Gnjatic

Li³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

320

246

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“…The broad and proinflamma-tory cytokine profile may mobilize the adaptive and the innate immune system. Interestingly, polyfunctional cytokine profiles have been associated with protective immunity in patients surviving HIV or Leishmania (46)(47)(48). Polyfunctional cytokine patterns may be particularly important in a cancer vaccine setting, where there is a need to overcome established tumor tolerance and transform the inflammatory milieu.…”

Section: Discussionmentioning

confidence: 99%

Telomerase Peptide Vaccination Combined with Temozolomide: A Clinical Trial in Stage IV Melanoma Patients

Kyte

Gaudernack

Dueland

et al. 2011

Clinical Cancer Research

101

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Purpose: The study is a proof-of-principle trial evaluating toxicity, immune response, and clinical response in melanoma patients after combined therapy with temozolomide and the telomerase peptide vaccine GV1001. Our previous GV1001 trials showed immune responses in approximately 60% of lung or pancreatic cancer patients. Experimental Design: Twenty-five subjects with advanced stage IV melanoma (M1B or M1C) received concomitant temozolomide and GV1001. Temozolomide was administered 200 mg/m2 orally for 5 days every fourth week, and GV1001 as eight injections over 11 weeks. Immune response was evaluated by delayed type hypersensitivity, T-cell proliferation, and cytokine assays. The immunologic responders continued monthly vaccination. Results: The treatment was well tolerated. A GV1001-specific immune response was shown in 18 of 23 evaluated subjects (78%). Patients developing long-term T-cell memory survived more than those rapidly losing their responses. The immune response exhibited several characteristics of possible clinical significance including high IFNγ/IL-10 ratios, polyfunctional cytokine profiles, and recognition of naturally processed antigens. Survival compared favorably with matched controls from a benchmark meta-analysis (1 year: 44% vs. 24%, 2 years: 16% vs. 6.6%). The clinical responses developed gradually over years, contrary to what is expected from chemotherapy. Five patients developed partial tumor regression and six more recorded stable disease. One patient has no remaining disease on fluorodeoxyglucose positron emission tomography scans after 5 years. Conclusions: The immunologic response rate is considerable compared with previous GV1001 trials without concomitant chemotherapy, although low toxicity is retained. The results warrant further studies of GV1001/temozolomide treatment and support the general concept of combining cancer vaccination with chemotherapy. Clin Cancer Res; 17(13); 4568–80. ©2011 AACR.

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“…Accordingly, CT7-specific CD4 + T cells were able to specifically kill peptide-pulsed melanoma cell line in a chromium release assay. Perforin-secreting CD4 + T cells have been previously described for the in vitro expanded MAGE-A3-specific CD4 + T cells (14) and in vivo for viral antigen-specific CD4 + T cells (38). Recently, two murine studies showed that cytolytic tumor-specific CD4 + T cells can egress to the tumor site and efficiently eradicate melanoma lesions when combined with additional treatments (39,40).…”

Section: Ct7-specific Cd4 + T-cell Clones Recognize Naturally Processmentioning

confidence: 99%

Fine analysis of spontaneous MAGE-C1/CT7–specific immunity in melanoma patients

Nuber

Curioni-Fontecedro

Matter

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Cancer/testis (CT) antigens represent prime candidates for immunotherapy in cancer patients, because their expression is restricted to cancer cells and germ cells of the testis. MAGE-C1/CT7 is a CT antigen that is highly expressed in several types of cancers. Spontaneous occurrence of CT7-specific antibodies was previously detected by SEREX screen in a melanoma patient. However, naturally occurring CT7-specific T-cell responses have thus far not been detected. Peripheral blood mononuclear cells (PBMCs) from 26 metastatic melanoma patients expressing CT7 in their tumor lesions (CT7 + ) were analyzed for CT7-specific T-cell responses using overlapping peptides. CT7-specific CD4 + T-cell responses were detected in three patients (11.5%). These CT7-specific CD4 + T-cell responses were detectable in melanoma patients' PBMCs exclusively from preexisting CD45RA − memory CD4 + T-cell pool. Additional CT7-specific memory CD4 + T-cell responses were detected in CT7 + melanoma patients after depletion of CD4 + CD25high Treg cells showing that Treg cells impact on CT7-specific CD4 + T cells in melanoma patients. CT7-specific CD4 + T-cell clones were generated and used to define minimal epitopes, restriction elements, and confirm the recognition of naturally processed antigen. Surprisingly, these clones were able to secrete perforin and exert cytotoxicity. This study shows that CT7 can induce specific cellular immunity in melanoma patients. Based on these findings, CT7 will be further explored as a potential vaccine for melanoma immunotherapy.cancer/testis antigens | T-cell response

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Polyfunctional T cell responses are a hallmark of HIV‐2 infection

Cited by 212 publications

References 50 publications

CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit

CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit

Telomerase Peptide Vaccination Combined with Temozolomide: A Clinical Trial in Stage IV Melanoma Patients

Fine analysis of spontaneous MAGE-C1/CT7–specific immunity in melanoma patients

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