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Tumor antigen

About: Tumor antigen is a research topic. Over the lifetime, 4438 publications have been published within this topic receiving 169624 citations.


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Journal ArticleDOI
20 Aug 2009-Blood
TL;DR: It is suggested that the tumor microenvironment can lead to up-regulation of PD-1 on tumor-reactive T cells and contribute to impaired antitumor immune responses.

1,497 citations

Journal ArticleDOI
TL;DR: The principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer is proved and evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression is provided.
Abstract: Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8+ cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8+ T cell infiltration, whereas nonregressing lesions lacked CD8+ T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression.

1,322 citations

Journal ArticleDOI
TL;DR: A gene encoding a melanocyte lineage-specific protein (MART-1) that is a widely shared melanoma antigen recognized by the T lymphocytes of patients with established malignancy is identified and opens possibilities for the development of immunotherapies for patients with melanoma.
Abstract: By cDNA expression cloning we have isolated a gene encoding a shared human melanoma antigen recognized by HLA-A2 restricted autologous and allogenic tumor-infiltrating lymphocytes (TILs) from patients with metastatic melanoma. By using both transient and stable expression systems, transfection of this gene into non-antigen-expressing HLA-A2+ cell lines resulted in recognition by the antigen-specific TILs. The sequence of this cDNA revealed a previously undescribed putative transmembrane protein whose expression was restricted to melanoma and melanocyte cell lines and human retina but no other fresh or cultured normal tissues tested or other tumor histologies. Thus, we have identified a gene encoding a melanocyte lineage-specific protein (MART-1; melanoma antigen recognized by T cells 1) that is a widely shared melanoma antigen recognized by the T lymphocytes of patients with established malignancy. Identification of this gene opens possibilities for the development of immunotherapies for patients with melanoma.

1,127 citations

Journal ArticleDOI
TL;DR: Developing and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors and initial clinical data indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL.
Abstract: We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver accumulation In tumor-bearing mice, DTXL-TNP exhibited markedly enhanced tumor accumulation at 12 hours and prolonged tumor growth suppression compared to a solvent-based DTXL formulation (sb-DTXL) In tumor-bearing mice, rats, and nonhuman primates, DTXL-TNP displayed pharmacokinetic characteristics consistent with prolonged circulation of NPs in the vascular compartment and controlled release of DTXL, with total DTXL plasma concentrations remaining at least 100-fold higher than sb-DTXL for more than 24 hours Finally, initial clinical data in patients with advanced solid tumors indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL, including pharmacokinetics characteristics consistent with preclinical data and cases of tumor shrinkage at doses below the sb-DTXL dose typically used in the clinic

1,029 citations

Journal Article
TL;DR: It is demonstrated that modifications that reroute a cytosolic tumor antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo therapeutic potency of recombinant vaccines.
Abstract: Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity. In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1). Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7. In the current study, we tested these recombinant vaccinia for in vivo protection against an E7+ tumor, TC-1, which was derived from primary epithelial cells of C57BL/6 mice cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes. All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection. Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden. These findings point out the therapeutic limitations of recombinant vaccinia expressing unmodified tumor antigens. Further, they demonstrate that modifications that reroute a cytosolic tumor antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo therapeutic potency of recombinant vaccines.

1,015 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202339
202222
2021166
2020203
2019181
2018150