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Context: We previously reported a novel tumour associated antigen (TTA) with molecular weight around 48 kDa and identified the novel TTA as a fragment derived from human DNA-topoiomerase I (TOP1). We termed the novel TAA as TOPO48 and termed autoantibody against the TAA as anti-TOPO48 autoantibody. Objective: To explore the clinical significance of anti-TOPO48 autoantibody in patients with colorectal carcinoma (CRC). Materials and methods: Serum levels of the autoantibody in patients with CRC or benign tumours and healthy volunteers were measured with a specific ELISA. Results: CRC patients at early stage had higher frequency of positive levels of the autoantibody and CRC patients with positive autoantibody levels had higher overall survival rate than those with negative autoantibody levels. Conclusion: The autoantibody is a potential biomarker for early diagnosis and favourable prognosis of CRC.

Background: The production of autoantibodies against tumour-associated antigens (TAAs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells. Over the past few decades, a number of different TAAs and their corresponding autoantibodies have been investigated. However, positive frequency of autoantibody detection in cancer patients has been relatively low. Here we describe a novel TAA that was a fragment derived from human DNA-topoiomerase I and an autoantibody against the novel TAA with relatively high positive frequency in the sera of early-stage non-small-cell lung cancer (NSCLC), gastric cancer (GC), colorectal cancer (CRC) and oesophageal squamous cell carcinoma (ESCC). Methods: Serologic enzyme-linked immunosorbent assay (ELISA) and western blot were used to discover a novel TAA with a molecular weight of 48 kDa separated by ion exchange chromatography. Autoantibody ELISA, immnohistochemistry and immunofluorescent staining, recombinant protein cloning/expression and western blot were used to identify the novel TAA. The association of the autoantibody against the novel TAA with early-stage carcinoma was explored by screening 203 stage I/II patients and 170 stage III/IV patients with NSCLC, GC, CRC or ESCC. Results: We identified the novel TAA as a fragment derived from human DNA-topoiomerase I (TOP1). We found that the novel TAA induced specific autoantibodies with a high prevalence that ranged from 58 to 72% in some of the most common types of cancer. We observed that the immune response against the novel TAA was associated with early stage ESCC, GC, CRC and NSCLC. Conclusions: The findings in this study suggest that the autoantibody against the novel TAA may be a potential biomarker for use in the early detection and diagnosis of cancer.

Background: The distinct expression pattern of tumour-associated antigens (TAAs) might be a critical reason for the inefficacy of immunity-based treatments and heterogeneous postsurgical recovery in patients with solid tumours, including hepatocellular carcinoma (HCC). However, little is known about the clinical value of the coexpression patterns of multiple TAAs. Methods: We determined the expression of multiple TAAs with identified immunogenicity (GPC3, AFP, SSX-2, NY-ESO-1, EpCAM, midkine) and the density of tumour-infiltrating immune cells by immunohistochemistry in a panel of 362 primary HCC patients. We evaluated the association between the TAAs, immune cell infiltration, clinicopathological parameters, and prognosis. Results: Patients who coexpressed more TAAs had better prognosis (P

In a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity.

The Wilms' tumour-1 (WT1) protein is considered a prime target for cancer immunotherapy based on its presumptive immunogenicity and widespread expression across a variety of malignancies. However, little is known about the naturally occurring WT1-specific T-cell repertoire because self-derived antigens typically elicit low frequency responses that challenge the sensitivity limits of current detection techniques. In this study, we used highly efficient cell enrichment procedures based on CD137, CD154, and pHLA class I tetramer staining to conduct a detailed analysis of WT1-specific T cells from the peripheral blood. Remarkably, we detected WT1-specific CD4(+) and CD8(+) T-cell populations in the vast majority of healthy individuals. Memory responses specific for WT1 were commonly present in the CD4(+) T-cell compartment, whereas WT1-specific CD8(+) T cells almost universally displayed a naive phenotype. Moreover, memory CD4(+) and naive CD8(+) T cells with specificity for WT1 were found to coexist in some individuals. Collectively, these findings suggest a natural discrepancy between the CD4(+) and CD8(+) T-cell lineages with respect to memory formation in response to a self-derived antigen. Nonetheless, WT1-specific T cells from both lineages were readily activated ex vivo and expanded in vitro, supporting the use of strategies designed to exploit this expansive reservoir of self-reactive T cells for immunotherapeutic purposes.

A radioimmunometric sandwich assay for the tumour-associated antigen defined by the monoclonal antibody (MAb) HMFG2, has been used to measure serum levels of the antigen in 76 healthy controls, 38 ovarian carcinoma patients pre-operatively, 98 patients 2 to 6 weeks after surgery and 36 patients at relapse or in complete remission at 12 months. HMFG2 antigen levels were elevated in 33% of stage-I and 62% of II-IV patients pre-operatively; they reflected bulk of disease post-surgically and were significantly higher in patients in relapse than in those who were in complete remission. HMFG2 antigen levels predicted the clinical course of disease in the majority of patients.

Xeno-antiserum specific for antigenic components of bronchogenic carcinoma was raised in rabbits, by passively immunizing them to normal human lung antigens at the same time as immunization with a tumour extract from a squamous-cell carcinoma. Antiserum so raised contained minimal quantities of anti-normal antibody which could be removed by a single absorption with glutaral-dehyde-insolubilized normal lung extract. When tested by quantitative complement fixation with a panel of tumour extracts from surgical specimens, it was found that the antiserum gave positive complement fixation with all squamous-cell carcinoma extracts tested, and with some of the extracts from bronchogenic carcinomas of differing pathological types. The antiserum was essentially negative for pooled extracts from normal lung, liver and spleen but gave a weak positive reaction with an extract of pooled foetal lung tissue.

Inbred rats were treated with extranuclear tumour membrane fractions or 3 M KCl-solubilized extracts of two antigenically distinct 3-methylcholanthreneinduced sarcomas, Mc7 and Mc57. The rats developed tumour-specific humoral antibody responses, but were not immune to tumour challenge. Moreover, they were unresponsive to subsequent immunization with irradiated tumour grafts, this effect being immunologically specific for the tumour from which the cell-free extracts was derived. in vitro studies revealed a depressed state of cell-mediated tumour immunity in animals inoculated with cell-free tumour extracts, and this was associated with the presence of serum inhibitory factors and suppressor lymphoid cells which abrogated the cytotoxic effect of sensitized lymphoid cells in vitro. It is postulated that the development of an inappropriate immune response due to the effect of tumour antigen during the induction phase of tumour immunity may be relevant to the immunobiology of tumour-bearing hosts. L'influence Des Preparations Acellulaires D'antigenes Associes A La Tumeur Sur Le Developpement De L'immunite Contre Les Tumeurs Chimio-Induites Chez Le Rat Des rats inbred ont ete traites au moyen de fractions de membranes tumorales extranucleaires ou d'extraits solubilises au KCl de deux sarcomes induits par le 3-methylcholanthrene et antigeniquement differents, Mc7 et Mc57. On a constate des reponses des anticorps humoraux specifiques de la tumeur, mais les animaux n'ont pas ete immunises contre celle-ci. De plus, ils n'ont pas reagi a une immunisation subsequente avec des greffes de tissu tumoral irradie, cet effet etant immunologiquement specifique pour la tumeur d'ou provenait l'extrait acellulaire. Des etudes in vitro ont indique que l'immunite a mediation cellulaire est deprimee chez les animaux inocules avec des extraits tumoraux acellulaires, et que cet etat est lie a la presence de facteurs inhibiteurs dans le serum et de cellules lymphoides a effet suppresseur qui annulent l'action cytotoxique des cellules lymphoides sensibilisees in vitro. L'auteur estime que, du point de vue de l'immunobiologie des hǒtes cancereux, il pourrait ětre interessant d'etudier le developpement d'une reponse immunitaire inappropriee sous l'effet de l'antigene tumoral pendant la phase d'induction de l'immunite.

Les taux seriques d'antigene CA 125 exprime par les cancers epitheliaux de l'ovaire ont ete doses chez 27 femmes menopausees presentant des tumeurs ovariennes et 16 temoins. On a observe des taux augmentes chez 9 (75%) des 12 patientes avec cancer ovarien; chez 3 patientes avec maladie au stade I les taux n'etaient pas augmentes. Aucune difference significative n'a ete trouvee pour les taux du sang veineux ovarien ou peripherique. Une baisse de taux d'antigene a ete observee 6-30 semaines apres intervention radicale et chimiotherapie cytostatique dans le groupe cancereux. Les resultats indiquent la valeur du dosage de CA 125 comme marqueur tumoral dans le suivi des cancers ovariens

The presence of Ca 125, an ovarian cancer-associated antigen, was assessed in serum from patients with liver diseases with (n = 26) and without (n = 26) ascites. Abnormal levels of serum CA 125 were observed in all patients with ascites and in 4 patients without ascites (15%). We conclude that CA 125 is a non-specific marker of ascites whatever the origin: ovarian carcinoma, cirrhosis or peritoneal inflammatory process.

Les auteurs rapportent deux techniques d'isolement de cellules hybrides humaines (cellules HeLa croisees avec des fibroblastes du derme) associees a des tumeurs radio-induites basees sur le fait que les cellules tumorales expriment selectivement une proteine de surface qui peut etre reconnue par un anticorps monoclonal. De telles techniques permettent un enrichisement rapide du milieu de culture

In this report we describe the preparation and partial characterization of a mono-specific anti-Wilms' antiserum raised in rabbits which had previously been injected normal kidney extracts in utero . The tumour associated antigen in Wilms' tumour does not appear to be oncofoetal antigen and it has also failed to react with feutin. It is possible that both our antiserum and that of Burtin and Gendron may be directed against a similar cell component.

TUMOUR-directed antibodies are found in the serum of patients suffering from malignant melanoma1–5, and so we have attempted to detect tumour-associated antigens in extracts from melanoma tumours and urine of patients.