Differential Expression of a New Tumor-Associated Antigen, TLP, During Human Colorectal Cancer Tumorigenesis

Guadagni, Fiorella; Graziano, Paolo; Roselli, Mario; Mariotti, Sabrina; Bernard, P; Vallebona, P Sinibaldi; Rasi, Guido; Garaci, Enrico

doi:10.1016/s0002-9440(10)65351-5

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…More than ten years ago a new TAA, the nonapeptide epitope CSH-275 (RTNKEASIC), was identified and we demonstrated its expression in tissue specimens from human CRC, while normal colonic mucosa was found to be negative. 42 CSH-275 expression was also correlated with the sequential stages of human CRC transformation. 42 Subsequently, the CSH-275 epitope was found to be naturally expressed in the DHD-K12 rat colon adenocarcinoma cell line.…”

Section: Action On Target Tumor Cellsmentioning

confidence: 91%

“…42 Subsequently, the CSH-275 epitope was found to be naturally expressed in the DHD-K12 rat colon adenocarcinoma cell line. 42,43 These cells, originally obtained from 1,2-dimethylhydrazine-induced colon adenocarcinoma in syngeneic immunocompetent BDIX rats, display many of the features of human epithelial cells constituting the CRC tissue, includ-ing not only the expression of the human TAA CSH-275 42,43 but also the constitutive activation of cancer-related pathways such as the Wnt/␤-catenin pathway, as recently demonstrated. 44 The features sustain the usefulness of this cell line as a suitable in vitro model for developing therapeutic strategies for CRC.…”

Section: Action On Target Tumor Cellsmentioning

confidence: 99%

“…This preclinical model, in which liver metastases are induced by injection of DHD-K12 cells in the splenic vein, closely mimics the clinical situation of metastatization after surgical resection of primary CRC, with high biological and immunological affinity to the human neoplasia. 42,43 This experimental model has been successfully used in our previous studies in which we assessed the antitumor activity of the triple combination therapy (T␣1 combined with IL-2 and 5 fluorouracil). 27 Using this animal model, we are performing a series of both in vivo and ex vivo experiments to determine whether T␣1 is capable of modulating the expression of the epitope CSH-275.…”

Section: Action On Target Tumor Cellsmentioning

confidence: 99%

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Thymosin α1 and cancer: action on immune effector and tumor target cells

Garaci¹,

Pica²,

Serafino³

et al. 2012

Annals of the New York Academy of Sciences

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Since it was first identified, thymosin alpha 1 (Tα1) has been characterized to have pleiotropic effects on several pathological conditions, in particular as a modulator of immune response and inflammation. Several properties exerted by Tα1 may be attributable to a direct action on lymphoid cells. Tα1 has been shown to exert an immune modulatory activity on both T cell and natural killer cell maturation and to have an effect on functions of mature lymphocytes, including stimulating cytokine production and cytotoxic T lymphocyte-mediated cytotoxic responses. In previous studies we have shown that Tα1 increases the expression of major histocompatibility complex class I surface molecules in murine and human tumor cell lines and in primary cultures of human macrophages. In the present paper, we describe preliminary data indicating that Tα1 is also capable of increasing the expression of tumor antigens in both experimental and human tumor cell lines. This effect, which is exerted at the level of the target tumor cells, represents an additional factor increasing the antitumor activity of Tα1.

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Section: Action On Target Tumor Cellsmentioning

confidence: 91%

Section: Action On Target Tumor Cellsmentioning

confidence: 99%

Section: Action On Target Tumor Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Thymosin α1 and cancer: action on immune effector and tumor target cells

Garaci¹,

Pica²,

Serafino³

et al. 2012

Annals of the New York Academy of Sciences

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“…Our model consists of a tumor naturally expressing a human TAA (CSH‐275) in immunocompetent syngeneic animals;21, 22, 23 this extremely simplifies the development of cancer vaccine models and their translation to clinical practice 46, 47. Furthermore, in this model, using a chemoimmunotherapeutic approach, the cure rate correlated with the number of CD4 + and CD8 + cells and not with the intensity of CTL activity 23, 24.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, we demonstrated expression of the nonapeptide epitope CSH‐275 (RTNKEASIC) in tissue specimens from colorectal cancer, while normal colonic mucosa was negative. CSH‐275 expression was also correlated with the various stages of human colorectal cancer transformation 21. Subsequently, the CSH‐275 epitope was found to be constitutionally expressed in DHD‐K12 tumor cells,22 which is an immunogenic rat colorectal carcinoma cell line 23.…”

mentioning

confidence: 95%

Vaccination with a synthetic nonapeptide expressed in human tumors prevents colorectal cancer liver metastases in syngeneic rats

Vallebona

Rasi

Pierimarchi

et al. 2004

Intl Journal of Cancer

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In previous studies, the antigen CSH-275 (RTNKEASIC) was found expressed in tissue specimens from colorectal cancer but not in normal colonic mucosa. It was also naturally expressed in the DHD-K12 experimental colorectal cancer in BDIX rats. In this study, we describe the effect of vaccination with the synthetic nonapeptide CSH-275 in preventing tumor growth in a model closely mimicking the clinical situation of liver metastases, after surgical resection of primary colorectal cancer. A vaccination protocol using CSH-275, conjugated with complete or incomplete Freund's adjuvant, was carried out to determine the effect in preventing the progression of liver metastases induced by DHD-K12 cells injected in the splenic vein (preventive vaccine). An additional vaccination procedure was carried out to determine the effect on s. Key words: cancer vaccine; peptide; liver metastasisThe identification of tumor antigens recognized by cellular or humoral effectors of the immune system has opened new possibilities for cancer therapy. One of the major applications of cancer antigens is the cancer vaccine. The molecular definition of several tumor antigens has opened the possibility of devising specific vaccination protocols based on the use of peptides, 1-5 and synthetic peptides may be particularly advantageous. 6 -8 A large number of clinical trials have demonstrated the feasibility of antitumor vaccinations and active immunotherapy with tumor-specific peptide vaccines. 4,9,10 Results are, however, variable: some tumors are easily rejected, whereas others escape destruction by the immune system. 11-14 This is probably due to the marked differences in the degree of immunogenicity between different tumors and the fact that colorectal cancer is regarded as refractive to conventional T-cell therapies. 15,16 Candidate immunodominant tumor antigens, providing the bases for antigen-specific vaccines, have been identified only for a limited number of tumors, such as melanoma and virus-associated tumors, 1,17,18 though a relevant number of tumor antigens have been characterized. 19,20 Moreover, in the majority of cases, tumor antigens are tumor-associated (TAA) rather than tumor-specific (TSA). 5,18,19 Therefore, the identification of specific epitopes remains one of the major problems in developing a vaccine approach, especially for epithelial tumors. 7,18 An ideal cancer vaccine should induce specific cytolytic immune activity against molecular targets expressed only on tumor cells, thus avoiding any damage to nonneoplastic cells.In previous studies, we demonstrated expression of the nonapeptide epitope CSH-275 (RTNKEASIC) in tissue specimens from colorectal cancer, while normal colonic mucosa was negative. CSH-275 expression was also correlated with the various stages of human colorectal cancer transformation. 21 Subsequently, the CSH-275 epitope was found to be constitutionally expressed in DHD-K12 tumor cells, 22 which is an immunogenic rat colorectal carcinoma cell line. 23 Injection of DHD-K12 cells in the splenic vein of syn...

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A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells

et al. 2000

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Renewed interest in cancer immunotherapy has been raised by the availability of a variety of tumor‐associated antigens and animal models. We have recently described the presence of a new antigen, TLP, in sera and cancer tissue from lung and colorectal cancer patients. In order to develop an experimental model suitable for preclinical studies on cancer vaccines, we investigated the presence of TLP antigen in vitro, in the DHD‐K12 cell line and in vivo, in metastases induced in syngeneic BDIX rats by DHD‐K12 cell injection. TLP was not detected in any tissue of healthy rats nor in normal tissues of tumor‐bearing rats. This is in agreement with our previous studies, in which we had demonstrated that TLP is expressed in human colorectal cancer and adenomas but not in normal colonic mucosa. Our results indicate TLP as a possible human tumor‐specific antigen naturally expressed in DHD‐K12 tumor syngeneic to immunocompetent BDIX rats. Int. J. Cancer 85:540–544, 2000. © 2000 Wiley‐Liss, Inc.

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Differential Expression of a New Tumor-Associated Antigen, TLP, During Human Colorectal Cancer Tumorigenesis

Cited by 10 publications

References 18 publications

Thymosin α1 and cancer: action on immune effector and tumor target cells

Thymosin α1 and cancer: action on immune effector and tumor target cells

Vaccination with a synthetic nonapeptide expressed in human tumors prevents colorectal cancer liver metastases in syngeneic rats

A new human tumor-associated antigen (TLP) is naturally expressed in rat DHD-K12 colorectal tumor cells

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