Tumor-rejection antigens recognized by T lymphocytes

Finn, Olivera J.

doi:10.1016/0952-7915(93)90124-b

Cited by 38 publications

(13 citation statements)

References 57 publications

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“…Many tumor-specific Ags identified to date have been characterized as proteins expressed differentially by tumor cells, which distinguishes them immunologically from normal cells. This differential expression may be the result of mutations in normal proteins, overexpression of normal proteins, or changes in the intracellular localization (2,4).…”

Section: The Mechanism Of Unresponsiveness To Circulating Tumormentioning

confidence: 99%

“…The Journal of Immunology, 2000, 165: 3730 -3741. O ne of the major goals of tumor immunology has been to find ways to enhance T cell responses to tumor Ags and incorporate these findings in the design of tumor-specific vaccines (1)(2)(3)(4)(5)(6). Knowledge of how tumor Ags are processed and presented by APCs is critical for understanding the initiation of immune responses against tumors and for the development of efficacious vaccines.…”

Section: The Mechanism Of Unresponsiveness To Circulating Tumormentioning

confidence: 99%

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The Mechanism of Unresponsiveness to Circulating Tumor Antigen MUC1 Is a Block in Intracellular Sorting and Processing by Dendritic Cells

Hiltbold¹,

Vlad²,

Ciborowski³

et al. 2000

The Journal of Immunology

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144

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Immunity to tumor Ags in patients is typically weak and not therapeutic. We have identified a new mechanism by which potentially immunogenic glycoprotein tumor Ags, such as MUC1, fail to stimulate strong immune responses. MUC1 is a heavily glycosylated membrane protein that is also present in soluble form in sera and ascites of cancer patients. We show that this soluble protein is readily taken up by dendritic cells (DC), but is not transported to late endosomes or MHC class II compartments for processing and binding to class II MHC. MUC1 uptake is mediated by the mannose receptor, and the protein is then retained long term in early endosomes without degradation. Long-term retention of MUC1 does not interfere with the ability of DC to process and present other Ags. We also demonstrate inhibited processing of another important glycoprotein tumor Ag, HER-2/neu. This may, therefore, be a frequent obstacle to presentation of tumor Ags and an important consideration in the design of cancer vaccines. It should be possible to overcome this obstacle by providing DC with a form of tumor Ag that can be better processed. For MUC1 we show that a 140-aa-long synthetic peptide is very efficiently processed by DC.

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Section: The Mechanism Of Unresponsiveness To Circulating Tumormentioning

confidence: 99%

Section: The Mechanism Of Unresponsiveness To Circulating Tumormentioning

confidence: 99%

The Mechanism of Unresponsiveness to Circulating Tumor Antigen MUC1 Is a Block in Intracellular Sorting and Processing by Dendritic Cells

Hiltbold¹,

Vlad²,

Ciborowski³

et al. 2000

The Journal of Immunology

Self Cite

144

View full text Add to dashboard Cite

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“…The transgenic (Tg) 3 mice expressing OVA 323-339 -specific I-A d -restricted TCR (DO11.10 TCR) maintained on the BALB/c background were kindly provided by Dr. T. Watanabe (Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan) (16). All the mice used were female and were used at 7-8 wk of age.…”

Section: Animalsmentioning

confidence: 99%

“…A ntigen-specific immune response plays a key role in immunity to pathogens or neoplasms (1)(2)(3). T cells bearing virus-or tumor-specific TCR have been used to establish the concept of adoptive immunotherapy, a possible choice for therapy.…”

mentioning

confidence: 99%

Functional Reconstitution of Class II MHC-Restricted T Cell Immunity Mediated by Retroviral Transfer of the αβ TCR Complex

Fujio

Misaki

Setoguchi

et al. 2000

The Journal of Immunology

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Transfer of the αβ TCR genes into T lymphocytes will provide a means to enhance Ag-specific immunity by increasing the frequency of tumor- or pathogen-specific T lymphocytes. We generated an efficient αβ TCR gene transfer system using two independent monocistronic retrovirus vectors harboring either of the class II MHC-restricted α or β TCR genes specific for chicken OVA. The system enabled us to express the clonotypic TCR in 44% of the CD4+ T cells. The transduced cells showed a remarkable response to OVA323–339 peptide in the in vitro culture system, and the response to the Ag was comparable with those of the T lymphocytes derived from transgenic mice harboring OVA-specific TCR. Adoptive transfer of the TCR-transduced cells in mice induced the Ag-specific delayed-type hypersensitivity in response to OVA323–339 challenge. These results indicate that αβ TCR gene transfer into peripheral T lymphocytes can reconstitute Ag-specific immunity. We here propose that this method provides a basis for a new approach to manipulation of immune reactions and immunotherapy.

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“…Such "tumor rejection antigens" (TRAs) are relatively rare, as the majority of molecular functions required for the survival and proliferation of neoplastic cells is shared with their non-transformed counterparts. 20,[251][252][253] At least in part, the emergence of antigenloss variants can be circumvent with vaccination strategies that simultaneously target several TAAs. As it stands, however, the identification of bona fide TRAs appears as a crucial goal for the development of next-generation peptide-based anticancer vaccines.…”

Section: Discussionmentioning

confidence: 99%