A New Era for Cancer Immunotherapy Based on the Genes that Encode Cancer Antigens

Rosenberg, Steven A.

doi:10.1016/s1074-7613(00)80028-x

Cited by 504 publications

(301 citation statements)

References 70 publications

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“…HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of HCC patients (Wang et al, 2002). Cancer/testis antigens are predominantly expressed in cancer tissues, but not in normal counterparts except in germ cells in testis or ovary (Wang et al, 2002), which has made them very useful in vaccine-based immunotherapy (Rosenberg, 1999).…”

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Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

et al. 2004

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Transduction of recombinant adenovirus into dendritic cells (DCs) is a promising new tool for cancer vaccine development. Here, we report that an adenovirus vector carrying hepatocellular carcinoma (HCC) antigen HCA661 and infected into DCs generates T-cell immunity against hepatoma cells. HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of an HCC patient. We constructed a recombinant adenovirus expressing the full-length cDNA of HCA661 gene and then transduced immature DCs, which had been generated with GM-CSF and IL-4 from peripheral blood mononuclear cell of HLA-A2 þ healthy donors. The resulting adenovirus-transduced DCs differentiated in the presence of monocyte-conditioned medium and poly [I] : poly [C], expressing the surface markers of mature DCs, including CD83, CD80, CD86 and HLA-DR. After maturation, the transduced DCs transcribed HCA661 mRNA and were able to prime the naïve T cells to become cytotoxic T lymphocytes (CTLs). Intracellular flow cytometry and enzyme-linked immunospot assay showed that these CTLs were able to target a hepatoma cell line, HepG2, which is HLA-A2 and HCA661 positive. In summary, we found that this recombinant adenovirus can help to induce DC maturation and these mature DCs can activate T cells to target hepatoma cells. Therefore, this recombinant adenovirus may have potential for use in liver cancer immunotherapy.

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Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

et al. 2004

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“…To overcome these problems, new therapeutic approaches including cancer immunogene therapy have recently been investigated. 2 Several reports have identified tumor-specific antigens for some tumors, and tumor-specific cytotoxic T cells (CTLs ) have been successfully isolated from patients with cancer. 3 However, most malignant tumors, including lung cancer, evade host immune surveillance.…”

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Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-γ gene into lung cancer

et al. 2001

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“…In the past decade many tumor antigens have been de®ned (reviewed by Old and Chen, 1998;Rosenberg, 1999).…”

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Human cortactin as putative cancer antigen

et al. 2000

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Humoral immune response against overexpressed oncogenic or tumor supressor proteins has been demonstrated for many types of cancer. In this study we report on the detection of the autologous antibody response to putative oncogene, human cortactin using serological analysis of breast carcinoma expression library. Cortactin maps to chromosome 11q13, the region ampli®ed in about 15% of primary breast carcinomas and 30% of head and neck squamous cell carcinomas. Cortactin overexpression due to such ampli®cation might a ect adhesive properties of human cancer cells and is associated with poor disease prognosis. Accordingly, we detected overexpression of cortactin transcript in autologous tumor and ampli®ca-tion/overexpression of cortactin in tumors of breast cancer patients serologically positive for this marker. We demonstrate that 15% of breast cancer patients elicit humoral immune response against human cortactin. Oncogene (2000) 19, 5204 ± 5207.Keywords: breast cancer; cortactin; cancer antigen; tumor markerThe development of cancer vaccines requires the identi®cation and characterization of tumor antigens. In the past decade many tumor antigens have been de®ned (reviewed by Old and Chen, 1998;Rosenberg, 1999).In 1991 T Boon and colleagues discovered the ®rst antigen recognized by cytotoxic T-lymphocytes (CTL) in human melanoma (van der Bruggen et al., 1991). In their study tumor antigens have been identi®ed by the transfection of cDNA libraries into cells expressing the appropriate MHC molecule followed by the identi®ca-tion of transfectant using cytokine release or lysis by human T cells with speci®c antitumor reactivity (Boon et al., 1994).An alternative technique for the identi®cation of tumor antigens has been reported by Sahin et al. (1995). This approach of serological analysis of cDNA expression libraries (SEREX), was based on previously described molecular screening techniques (D'Arpa et al., 1988) and exploited patient's B-cell repertoire for the identi®cation of human tumor antigens that show immunogenicity in the autologous host. Many antigens have been isolated by this technique, demonstrating that most, if not all, human cancers express multiple antigens including ampli®ed/overexpressed proteins with known cancer association (reviewed by Old and Chen, 1998;Disis and Cheever, 1996;Brass et al., 1999).In this study we applied the SEREX method to isolate and characterize candidate tumor antigens expressed in breast carcinoma. A cDNA library in phage expression vector (lambda ZAP Express) was prepared from a surgical tumor specimen of a 56-yearold woman with ER-positive breast carcinoma (T 1 M 0 N 0 ). The library was plated and screened with autologous patient's serum diluted 1 : 200 as previously described (Scanlan et al., 1998). Screening of 3610 5 primary recombinant phage clones yielded a total of 70Oncogene (2000) 19, 5204 ± 5207 ã 2000 Macmillan Publishers Ltd All rights reserved 0950 ± 9232/00 $15.00 www.nature.com/onc The deduced amino acid sequence of MOBr-140 represents human cortactin from a...

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A New Era for Cancer Immunotherapy Based on the Genes that Encode Cancer Antigens

Cited by 504 publications

References 70 publications

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-γ gene into lung cancer

Human cortactin as putative cancer antigen

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