Reverse ELISPOT assay for clonal analysis of cytokine production I. Enumeration of gamma-interferon-secreting cells

Czerkinsky, Cécil; Andersson, Gunnel; Ekre, Hans-Peter; Nilsson, Lars‐Åke; Klareskog, Lars; Ouchterlony, Örjan

doi:10.1016/0022-1759(88)90079-8

Cited by 464 publications

(204 citation statements)

References 28 publications

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“…In the further phase II trial, cellular immunity will be assessed by ELISPOT and Tetramer methods in certain patients with a defined tumor. 35,36 In conclusion, H103 is well tolerated and can be safely administered by intratumoral injection and displays oncolytic activity at a total dose of 3.0 Â 10 12 VP as evidenced by local partial response responses. The results of this study suggest a potential role for this in vivo personalized vaccination strategy against tumors.…”

Section: Discussionmentioning

confidence: 88%

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients

Li¹,

Liu

Xr³

et al. 2008

Gene Ther

105

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Our pre-clinical studies demonstrated that intratumoral vaccination with a recombinant oncolytic type 2 adenovirus overexpressing the heat shock protein (HSP)70 protein, designated as H103, can inhibit primary and metastatic tumors through enhanced oncolytic activity and HSPmediated immune responses against shared and mutated tumor antigens. In the pre-clinical studies of local H103 administration, no significant toxicity was observed in the animal trials with mice, cavy or rhesus monkeys. A phase I clinical trial of intratumoral injection of H103 was conducted in the patients with advanced solid tumors. A total of 27 patients were injected intratumorally with H103 in a dose-escalation study from a dose of 2.5 Â 10 7 to 3.0 Â 10 12 viral particles (VPs). The maximum tolerated dose of H103 was not defined. Two patients developed dose-limiting toxicities of grade III fever at the dose of 1.5 Â 10 12 VP and transient grade IV thrombocytopenia at the dose of 3.0 Â 10 12 VP. The common adverse events were mainly mild to moderate (grade I/II) in nature, including fever, mild injection-site reaction, leucopenia, lymphopenia, thrombocytopenia and hypochromia. The objective response (complete response+partial response) to H103-injected tumors was 11.1% (3/27), and the clinical benefit rate (complete response+partial response+minor response+stable disease) was 48.1%. Interestingly, transient and partial regression of distant, uninjected tumors was observed in three patients. The numbers of immune cells (CD4 + and CD8 + T cells, and natural killer cells) were elevated after H103 administration, but without statistical significance. This phase I trial demonstrates that intratumoral administration of H103 can be safely applied to cancer patients and shows promising clinical antitumor activity, warranting a further clinical investigation.

show abstract

Section: Discussionmentioning

confidence: 88%

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients

Li¹,

Liu

Xr³

et al. 2008

Gene Ther

105

View full text Add to dashboard Cite

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“…Two commercial forms of the IFNGRA are now variously licensed for use in the developed world: the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), which is based on the enzymelinked immunospot (ELISpot) assay (14); and the whole bloodbased QuantiFERON-TB Gold (QFT-G; Cellestis, Melbourne, Australia), which uses an ELISA to detect IFN-␥ released into culture supernatant (15). Most data that supported licensing and introduction of these tests were obtained from studies in regions of the world where tuberculosis is uncommon and with emphasis on HIV-uninfected persons.…”

Section: What This Study Adds To the Fieldmentioning

confidence: 99%

Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

Rangaka¹,

Wilkinson²,

Seldon³

et al. 2007

Am J Respir Crit Care Med

186

152

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“…Salmonella-specific ELISPOT and ELISA Salmonella-specific IFN-␥-producing cells were quantified using the ELIS-POT assay (28). Spleens were harvested from Salmonella-infected and uninfected mice, a single cell suspension was prepared, RBC were lysed, and remaining cells counted.…”

Section: Salmonella-specific Serum Ab Responsesmentioning

confidence: 99%

Expression of T-bet by CD4 T Cells Is Essential for Resistance toSalmonellaInfection

Ravindran

Foley

Stoklasek

et al. 2005

The Journal of Immunology

138

145

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Despite the recognized role of the T-bet transcription factor in the differentiation of Th1 cells, T-bet-deficient mice can develop small numbers of IFN-γ-producing CD4 T cells. Although these are not sufficient to allow normal handling of some pathogens, T-bet-deficient mice do resolve infection with the intracellular pathogen Listeria monocytogenes. In contrast, we report that expression of T-bet is required for resistance to Salmonella infection. T-bet-deficient mice succumbed to infection with attenuated Salmonella and did not generate IFN-γ-producing CD4 T cells or isotype-switched Salmonella-specific Ab responses. Spleen cells from Salmonella-infected T-bet-deficient mice secreted increased levels of IL-10, but not IL-4, upon in vitro restimulation. A Salmonella-specific TCR transgenic adoptive transfer system was used to further define the involvement of T-bet expression in the development of Salmonella-specific Th1 cells. Wild-type Salmonella-specific CD4 T cells activated in T-bet-deficient recipient mice displayed no defect in clonal expansion, contraction, or IFN-γ production. In contrast, T-bet-deficient, Salmonella-specific CD4 T cells activated in wild-type recipient mice produced less IFN-γ and more IL-2 upon in vivo restimulation. Therefore, expression of T-bet by CD4 T cells is required for the development of Salmonella-specific Th1 cells, regulation of IL-10 production, and resistance to Salmonella infection.

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Reverse ELISPOT assay for clonal analysis of cytokine production I. Enumeration of gamma-interferon-secreting cells

Cited by 464 publications

References 28 publications

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients

A phase I trial of intratumoral administration of recombinant oncolytic adenovirus overexpressing HSP70 in advanced solid tumor patients

Effect of HIV-1 Infection on T-Cell–based and Skin Test Detection of Tuberculosis Infection

Expression of T-bet by CD4 T Cells Is Essential for Resistance toSalmonellaInfection

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