Effect of B7.1-transfected human colon cancer cells on the induction of autologous tumour-specific cytotoxic T cells

Miyazono, Yuko; Kamogawa, Yumiko; Ryo, Kyouka; Furukawa, T.; Mitsuhashi, Maki; Yamauchi, Katsumi; Kameoka, Takanobu; Hayashi, Naoaki

doi:10.1046/j.1440-1746.1999.01990.x

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…Cell-mediated immunity elicited by MHC-associated antigens expressed on human tumors and recognized by cytotoxic T lymphocytes has been demonstrated for ovarian 7 and a number of other cancers. − To characterize the repertoire of T-cell-inducing antigens in ovarian cancer, we assessed MHC class I-restricted peptide epitopes obtained directly from the surfaces of ovarian cancer cells and analyzed by mass spectrometry. The data indicate that a number of autoantigens that induce autoantibody response also go through the MHC class I pathway and thus are potential T-cell targets (Tables −3).…”

Section: Discussionmentioning

confidence: 99%

“…2 Autoantigens represent a variety of intracellular and surface proteins, including differentiation antigens and other proteins that are overexpressed in tumors. 1,[3][4][5][6] The clinical application of cancer immunotherapy is based on growing evidence that cytotoxic T lymphocytes (CTL) can recognize and mount an effective attack against a wide variety of tumor cells that display specific TAA in the context of major histocompatibility complex (MHC) molecules on their surfaces, including ovarian 7 and colon tumors, [8][9][10][11][12][13][14] sarcomas, 15 renal cell carcinomas, 16 pancreatic tumors, 17 adenocarcinomas, and squamous tumors of the head and neck 18 and the lung. 19 When delivered in a system designed to elicit a strong T-cell response, MHC-associated antigens have the potential to break tolerance and stimulate an immune response to prevent metastatic disease progression and to generate a therapeutic response that can eliminate tumor cells in a cancer patient.…”

Section: Introductionmentioning

confidence: 99%

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Shared Immunoproteome for Ovarian Cancer Diagnostics and Immunotherapy: Potential Theranostic Approach to Cancer

et al. 2007

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Elimination of cancer through early detection and treatment is the ultimate goal of cancer research, and is especially critical for ovarian and other forms of cancers typically diagnosed at very late stages and that have very poor response rates. Proteomics has opened new avenues for the discovery of diagnostic and therapeutic targets. Immunoproteomics, which defines the subset of proteins involved in the immune response, holds considerable promise for providing a better understanding of the early stage immune response to cancer as well as important insights into antigens that may be suitable for immunotherapy. Early administration of immunotherapeutic vaccines can potentially have profound effects on prevention of metastasis and may potentially cure through efficient and complete tumor elimination. We developed a mass-spectrometry-based method to identify novel autoantibody-based serum biomarkers for the early diagnosis of ovarian cancer that uses native tumor-associated proteins immunoprecipitated by autoantibodies from sera obtained from cancer patients and from cancer-free controls to identify autoantibody signatures that occur at high frequency only in cancer patient sera. Interestingly, we identified a subset of more than 50 autoantigens that were also processed and presented by MHC class I molecules on the surfaces of ovarian cancer cells and thus common to the two immunological processes of humoral and cell-mediated immunity. These shared autoantigens were highly representative of families of proteins with roles in key processes in carcinogenesis and metastasis, such as cell cycle regulation, cell proliferation, apoptosis, tumor suppression and cell adhesion. Autoantibodies appearing at the early stages of cancer suggest that this detectable immune response to the developing tumor can be exploited as early stage biomarkers for the development of ovarian cancer diagnostics. Correspondingly, because the T cell immune response depends on MHC class I processing and presentation of peptides, the identification of proteins that go through this pathway are potential candidates for the development of immunotherapeutics designed to activate a T cell immune response to cancer. To the best of our knowledge, this is the first comprehensive study that identifies and categorizes proteins that are involved in both humoral and cell-mediated immunity against ovarian cancer, and may have broad implications for the discovery and selection of theranostic molecular targets for cancer therapeutics and diagnostics in general.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Shared Immunoproteome for Ovarian Cancer Diagnostics and Immunotherapy: Potential Theranostic Approach to Cancer

et al. 2007

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“…Several reports have indicated that CD80 geneinfected tumor cells can stimulate PBMC activity as effector cells [29,30]. CD80 delivers an important costimulatory signal via binding to its receptor, CD28 and CTLA-4 [29,31,32]. Cancer cells can escape from preexisting CTLs either by a loss of tumor antigen or by down-regulation of costimulatory molecules.…”

Section: Discussionmentioning

confidence: 99%

A Synergistic Antitumor Effect of Interleukin-2 Addition with CD80 Immunogene Therapy for Peritoneal Metastasis of Gastric Carcinoma

et al. 2007

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The co-stimulatory molecule CD80 is a ligand of CD28, which plays a key role in the induction of cell-mediated immune responses. Many tumors, including gastric cancer, decrease the expression of CD80, which results in the failure of immune recognition. We evaluated the effect of interleukin-2 addition combined with CD80 infection on the peritoneal metastasis in gastric cancer. CD80 infection combined with interleukin-2 addition significantly increased the activated cytotoxicity of mononuclear cells compared to CD80 gene infection and compared to the lacZ control group. In vivo, the survival of animals with intraperitoneal tumor was longest in those given CD80 infection with interleukin-2 addition (median survival, 46 days), followed by those given interleukin-2 (39 days), those given CD80 infection (37 days), and those given lacZ (29 days). These results suggest that interleukin-2 addition might contribute to improving the observed outcome of CD80 immunogene therapy in peritoneal metastasis of gastric carcinoma.

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“…CW2 cells were obtained from a 60-year-old female who underwent the surgical removal of colon cancer, and whose case was described (8). The cell line was maintained in medium consisting of RPMI-1640 (Thermo Fisher Scientific, Inc., Waltham, MA, USA) containing 10% heat-inactivated fetal bovine serum (Thermo Fisher Scientific, Inc.), 100 U/ml penicillin and 100 µg/ml streptomycin.…”

Section: Methodsmentioning

confidence: 99%

RT-qPCR analysis of the tumor antigens TOMM34 and RNF43 in samples extracted from paraffin-embedded specimens of colorectal cancer

et al. 2017

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Comprehensive genetic analysis of colorectal malignant tumors by microarrays has identified translocase of the outer mitochondrial membrane 34 (TOMM34) and ring finger protein 43 (RNF43) as highly expressed oncogenes in malignant colorectal tumors. Vaccine therapy using cancer peptides synthesized using the amino acid sequences of tumor antigens is currently undergoing clinical trials. Since it is important to perform vaccine therapy based on the oncogene expression levels in individual tumors, analysis of tumor antigen expression is necessary for this therapy. However, the quality of the messenger RNA extracted from formalin-fixed and paraffin-embedded specimens is generally considered insufficient for gene quantification. The present study examined whether it could be possible to quantify the expression of TOMM34 and RNF43 in colorectal cancer and liver metastasis samples prepared from paraffin blocks. The formalin-fixed and paraffin-embedded specimens were sliced for slides and the colorectal cancer and normal mucosal tissues were obtained from the slides. Total RNA was extracted from the tissue samples, and quantitative polymerase chain reaction (qPCR) was performed using the Universal ProbeLibrary as a PCR probe. Quantification of TOMM34 and RNF43 gene expression in several-year-old paraffin-embedded colorectal cancer specimens was possible by qPCR using the Universal ProbeLibrary. qPCR revealed that TOMM34 expression was elevated in 78.9% (15 of 19 cases) of the primary tumors and in 73.7% (14 of 19 cases) of the liver metastasis samples. RNF43 expression was elevated in 63.2% (12 of 19 cases) of the primary tumors and in 73.7% (14 of 19 cases) of the liver metastasis samples.

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Effect of B7.1-transfected human colon cancer cells on the induction of autologous tumour-specific cytotoxic T cells

Abstract: Thus, our results demonstrate that, by using B7.1 gene-transfected tumour cell lines, we effectively induced autologous tumour-specific CTL. These results will provide us with new tools for adoptive immunotherapy for colon cancer patients.

Cited by 8 publications

References 27 publications

Shared Immunoproteome for Ovarian Cancer Diagnostics and Immunotherapy: Potential Theranostic Approach to Cancer

Shared Immunoproteome for Ovarian Cancer Diagnostics and Immunotherapy: Potential Theranostic Approach to Cancer

A Synergistic Antitumor Effect of Interleukin-2 Addition with CD80 Immunogene Therapy for Peritoneal Metastasis of Gastric Carcinoma

RT-qPCR analysis of the tumor antigens TOMM34 and RNF43 in samples extracted from paraffin-embedded specimens of colorectal cancer

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