Genetic changes occurring in established tumors rapidly stimulate new antibody responses

Spiotto, Michael T.; Reth, Michael; Schreiber, Hans

doi:10.1073/pnas.0930140100

Cited by 16 publications

(16 citation statements)

References 35 publications

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“…The identification of EGFP 200 -208 as an H-2Kd-restricted cytotoxic-T-lymphocyte (CTL) epitope by Gambotto et al (2000) further defined EGFP as a model tumour antigen. Other workers have found that implantation of EGFP-expressing tumours in mice has induced the presence of anti-EGFP IgG antibodies in the serum (Brown et al, 2001;Spiotto et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

2006

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The ideal cancer treatment should both destroy the primary tumour and at the same time educate the immune system to recognise the tumour as foreign so that distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the i.v. administration of photosensitisers followed by illumination of the tumour with red light producing reactive oxygen species that eventually cause vascular shutdown and tumour cell death by apoptosis and necrosis. Anti-tumour immunity is stimulated after PDT due to the acute inflammatory response, generation of tumour-specific antigens, and induction of heat-shock proteins. Green fluorescent protein (GFP) is used as an optical reporter to noninvasively image the progression of mouse tumours, and in addition, may act as a foreign (jellyfish) antigen. We asked whether GFP-expressing tumours could be used to monitor the response of tumour-bearing mice to PDT, and whether the tumour response differed when a nonimmunogenic tumour cell line was transduced with GFP. We injected RIF-1 or RIF-1 EGFP (stably transduced with a retroviral vector) cells in the leg of C3H/HeN mice and both the cells and tumour grew equally well. We used PDT with benzoporphyrin derivative and a short drug-light interval. There were complete cures and 100% mouse survival of RIF-1 EGFP while RIF-1 wild-type tumours all recurred. Cured mice were resistant to rechallenge with RIF-1 EGFP cells and a rechallenge with wild-type RIF-1 cells grew significantly slower. There was also slower RIF-1 EGFP rechallenge growth but no rejection when RIF-1 EGFP tumours were surgically removed. There was a low rate of PDT cure of tumours when RIF-1 cells were transduced with an empty retroviral vector. The presence of antibodies against EGFP in mouse serum suggests EGFP can act as a foreign antigen and PDT can then stimulate a long-term memory immune response.

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Section: Discussionmentioning

confidence: 99%

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

2006

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“…These mutant self-Ags can contribute to tumorigenesis, but different mutations are typically found in different examples of a particular type of tumor (50). In contrast, many of the alterations that are shared among tumors and are likely to drive different components of carcinogenesis represent normal, nonmutated self-Ags (51)(52)(53)(54)(55).…”

Section: Classes Of Tumor Agsmentioning

confidence: 99%

Dendritic Cell Targeting of Survivin Protein in a Xenogeneic Form Elicits Strong CD4+ T Cell Immunity to Mouse Survivin

Charalambous

Oks

Nchinda

et al. 2006

The Journal of Immunology

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To determine whether strong CD4+ T cell immunity could be induced to a nonmutated self protein that is important for tumorigenesis, we selectively targeted the xenogeneic form of survivin, a survival protein overexpressed in tumors, to maturing dendritic cells in lymphoid tissues. Dendritic cell targeting via the DEC205 receptor in the presence of anti-CD40 and poly(I:C) as maturation stimuli, induced strong human and mouse survivin-specific CD4+ T cell responses, as determined by IFN-γ, TNF-α, and IL-2 production, as well as the development of lytic MHC class II-restricted T cells and memory. Immunity was enhanced further by depletion of CD25+foxp3+ cells before vaccination. anti-DEC205-human survivin was superior in inducing CD4+ T cell responses relative to other approaches involving survivin plasmid DNA or survivin peptides with adjuvants. However, we were unable to induce CD8+ T cell immunity to survivin by two doses of DEC205-targeted survivin or the other strategies. Therefore, significant CD4+ T cell immunity to a self protein that is overexpressed in most human cancers can be induced by DEC205 targeting of the Ag in its xenogeneic form to maturing DCs.

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“…Recent studies have defined specific antibody responses to tumour-related antigens in patients with cancer 4 5 6 7 8. Since these antibodies are often triggered by changes in the structure or expression of self proteins in tumour cells,9 10 they may serve as potential immunological markers of cancer 11 12…”

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confidence: 99%

Human IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer

Kijanka

Hector

Kay

et al. 2009

Gut

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Genetic changes occurring in established tumors rapidly stimulate new antibody responses

Abstract: Cre-loxP ͉ immunosurveillance ͉ EGFP ͉ SEREX ͉ cancer

Cited by 16 publications

References 35 publications

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

A green fluorescent protein-expressing murine tumour but not its wild-type counterpart is cured by photodynamic therapy

Dendritic Cell Targeting of Survivin Protein in a Xenogeneic Form Elicits Strong CD4+ T Cell Immunity to Mouse Survivin

Human IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer

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