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Tumour Antigens (tumour + antigen)
Selected AbstractsVakzinationstherapie kutaner T-Zell-LymphomeJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 12 2002Vaccination therapy for cutaneous T-cell lymphoma primary cutaneous T cell lymphomas (CTCL); vaccination; antigenic targets Zusammenfassung: Primär kutane T-Zell-Lymphome (CTCL) sind definiert als klonale Proliferation hautinfiltrierender T-Lymphozyten. Unabhängig von der Heterogenität dieser Krankheitsgruppe besteht derzeit keine kurative Therapiemöglichkeit, was zur Entwicklung verschiedener Behandlungsstrategien, einschließlich der Vakzination, führte. Dieser Artikel gibt eine Übersicht über den Entwicklungsstand der Vakzinationstherapie für Lymphome mit besonderer Rücksicht auf die CTCL. Da bisher kein universelles Tumorantigen identifiziert wurde, sind verschiedenste antigene Agenzien (komplette Tumorzellen, Idiotypen, Cancer/Testis-Antigene, Proteine aus tumorassoziierten Mutationen und Mimotope) hinsichtlich ihrer Eignung für die Vakzinationstherapie von CTCL untersucht worden. Die antigene Information dieser Präparationen kann dem körpereigenen Immunsystem über verschiedene Wege (Carrier) dargeboten werden, bisher sind dazu mit Tumorzellen fusionierte dendritische Zellen, Idiotyp-Proteine oder -Peptide sowie DNA- und RNA-Präparationen eingesetzt worden. Da die verwendeten Antigene allesamt schwache Immunogene darstellen, sind Adjuvanzien (dendritische Zellen, immunogene Peptide, Oligonukleotide, Zytokine, virale Vektoren) notwendig, um eine suffiziente Antigenpräsentation und Aktivierung des Immunsystems zu erreichen. Erste klinische Daten bestätigen die prinzipielle Wirksamkeit einer Vakzinationstherapie bei CTCL. Die große Anzahl bisher verwendeter Antigene, Carrier, Adjuvanzien und Applikationsschemen macht die Identifizierung eines optimalen Protokolls jedoch nahezu unmöglich. Da auch die Wechselwirkungen zwischen Lymphom und Immunsystem sehr komplex und nicht vollständig verstanden sind, ist bis zur Einführung der Vakzinationstherapie in die klinische Praxis noch großer Forschungsaufwand nötig. Summary: Primary cutaneous T,cell lymphomas (CTCL) are defined as clonal proliferation of skin-infiltrating T lymphocytes. Despite their heterogeneity, CTCL are generally incurable, which lead to the development of various treatment strategies including vaccination. Here, the attempts to vaccinate against lymphoma will be reviewed with special emphasis on CTCL. Since an universal tumour antigen is not available so far, different targets, including whole tumour cells, idiotypes, cancer/testis antigens, proteins derived from tumour-associated mutations, and mimotopes, have been investigated for their applicability in CTCL vaccination. The antigenic information can be delivered in different ways. So far, tumour cells fused to dendritic cells, idiotypic proteins/peptides and DNA/RNA preparations have been applied in lymphoma. Since most targets are weak immunogens, adjuvants and other helpers, including dendritic cells, immunogenic peptides and oligonucleotides, cytokines, and viral vectors, are required to enable proper presentation of the antigens and sufficient activation of the immune system. Although first data from CTCL patients prove the suitability of vaccination in CTCL therapy, the number of available antigens, carriers, adjuvants and application schemes creates a multitude of vaccine formulations and identification of the best-suited approach difficult. Furthermore, the relationship between lymphoma and the host immune system is complex and still not completely understood. In consequence, CTCL vaccination requires a lot of research to be done before its breakthrough. [source] A comparison of urinary nuclear matrix protein-22 and bladder tumour antigen tests with voided urinary cytology in detecting and following bladder cancer:the prognostic value of false-positive resultsBJU INTERNATIONAL, Issue 7 2001V. Poulakis Objectives To evaluate the diagnostic and prognostic value of the nuclear matrix protein-22 (NMP22) and bladder tumour antigen (BTAstat) tests compared with voided urinary cytology (VUC) in detecting and following bladder cancer, assessing particularly the prognostic value of false-positive test results in patients followed up for bladder cancer. Patients and methods From 739 patients suspected of having bladder cancer, voided urine samples for the NMP22 and BTAstat tests, and for VUC and urine analysis, were collected before cystoscopy. All patients underwent transurethral resection of bladder lesions or mapping, and were followed for a mean (range) of 27.3 (3,65) months. Results In the 406 patients with bladder cancer, the overall sensitivity was 85% for NMP22, 70% for BTAstat and 62% for VUC. For histological grades 1,3 the sensitivity in detecting transitional cell carcinoma was 82%, 89% and 94% for NMP22, 53%, 76% and 90% for BTAstat, and 38%, 68% and 90% for VUC, respectively. Although the sensitivity in detecting invasive carcinoma was > 85% for all the tests, NMP22 and BTAstat were statistically more sensitive than VUC for superficial tumours. The optimal threshold value for NMP22, calculated using the receiver operating characteristics curve, was 8.25 U/mL. The specificity was 68% for NMP22, 67% for BTAstat, and 96% for VUC. The specificity of VUC remained > 87% and was independent of benign histological findings. In contrast, in patients with no apparent genitourinary disease on histology, NMP22 and BTAstat had significantly higher specificity (94% and 92%, respectively; P = 0.003) than in the group with chronic cystitis (52% for both tests). Forty patients having no bladder cancer at biopsy had a recurrence after a mean (range) follow-up of 7.7 (3,15) months; all had a previous history of bladder cancer. According to subsequent recurrence, the prognostic positive and negative predictive values were 18% and 91% for NMP22, 13% and 88% for BTAstat, and 79% and 91% for VUC. Both false-positive VUC and NMP22 tests predicted recurrence (log-rank test, P < 0.001 and P = 0.004, respectively), but the BTAstat test produced no similar correlation (P = 0.778). Conclusion The NMP22 and BTAstat tests are better than VUC for detecting superficial and low-grade bladder cancer but they have significantly lower specificity. After excluding diseases with the potential to interfere in these tests the overall specificity of both tests is increased considerably. False-positive results from NMP22 and VUC but not from BTAstat in patients followed up for bladder cancer correlate with future recurrences. [source] Dendritic cell vaccination and immune monitoringISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue 1 2009E. H. J. G. Aarntzen Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. Following infection or inflammation, they undergo a complex process of maturation and migrate to lymph nodes where they present antigens to T cells. Their decisive role in inducing immunity formed the rationale for DC immunotherapy: DCs loaded with tumour antigens are injected into cancer patients to stimulate T cells to eradicate tumours. Effective immune responses and favourable clinical outcomes have indeed been observed, but only in a minority of patients. Therefore, it is obvious that current DC-based protocols need to be improved. For this reason, we study in small proof-of-principle trials the fate, interactions and effectiveness of the injected DC. The success of DC-based immunotherapy to induce cellular immunity against tumours is highly dependent on accurate delivery and trafficking of the DC to T cell-rich areas of secondary lymphoid tissues. [source] Targeted immunotherapy of cancer: development of antibody-induced cellular immunityJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2003Yingjuan Lu ABSTRACT Although immunotherapy of cancer encompasses a large variety of distinct protocols, virtually all therapeutic strategies require the enabling/training of the immune system to distinguish tumour tissue from healthy tissue. In the case of antibody-based therapies, specificity obviously arises from the selectivity of the antibodies for tumour antigens, and tumour cell death derives from either direct cytotoxicity of the antibody or antibody-dependent cellular cytotoxicity. However, even when both of the above killing mechanisms are simultaneously active, we suggest that antibody-based immunotherapies may fall far short of their full potential. In this editorial, we first summarize the mechanisms by which current antibody-based therapies mediate cancer cell removal, and then propose two strategies by which this class of immunotherapies might be further improved. These suggested improvements involve the decoration of tumour cell surfaces with foreign haptens against which an endogenous humoral immune response can be mounted and the recruitment of the cellular arm of the immune system in an antibody-dependent process. [source] SEREX identification of new tumour-associated antigens in cutaneous T-cell lymphomaBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2004T.B. Hartmann Summary Background Cutaneous T-cell lymphoma (CTCL) is a clonal lymphoproliferative disorder of mainly CD4+ T cells, with primary manifestation in the skin. Objectives To detect new CTCL-associated antigens for immunological therapies and to define their specificity in terms of RNA expression and seroreactivity. Methods A newly constructed CTCL cDNA phage library was screened and cross-reactivities against the detected clones were tested using 15 mycosis fungoides and six Sézary syndrome sera. The mRNA expression of the identified genes was analysed by reverse transcription,polymerase chain reaction (RT,PCR) using 22 tumour tissues, nine cell lines and up to 29 different types of normal tissue. Results We identified nine different tumour antigens (HD-CL-01 to HD-CL-09) of which seven clones had high homology to genes with known functions. Several of these genes had previously been associated with cancer, namely inositol 1,4,5-triphosphate 5-phosphatase, vimentin, aldose reductase and elongation factor-1,. Variations in the deduced protein sequences were observed in three cases, mostly due to variations in protein length. The individual clones were recognized by up to 56% of patients' sera, while control sera were negative except in one case. Using RT,PCR, we found a frequent expression of these new tumour antigens in tumour specimens (26,100%). In contrast to humoral specificity, specific mRNA was also detected in selected normal tissues (29,89%). Conclusions SEREX (serological identification of antigens by recombinant expression cloning) identified multiple tumour-associated antigens in CTCL. The serological specificity and the high percentage of reactive sera of CTCL patients against several clones suggest these genes as potential targets for diagnostic and prognostic purposes. [source] Seroreactivity against MAGE-A and LAGE-1 proteins in melanoma patientsBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2003D. Usener Summary Background Cancer-testis antigens exemplify a growing number of tumour antigens which are expressed in a variety of malignancies, but not in normal tissues other than germ cells, primarily those of the testis. Objectives To investigate the humoral response to known cancer-testis antigens in melanoma patients. Methods We used phage clones coding for seven different melanoma antigens MAGE-A or LAGE-1A proteins. These clones were isolated using the newly developed DNA hybridization analysis of recombinantly expressed cDNA libraries (HYREX) approach. HYREX combines the advantage of a nonradioactive library screening method with the possibility of subsequently analysing the serological response to the recombinant proteins. We isolated clones coding for MAGE-A1, -A3, -A4b, -A6, -A9 and -A12, as well as LAGE-1A. Additionally, we correlated gene expression and seroreactivity. Results Between 13% and 27% of sera (n = 15) were reactive against individual tumour antigens. We found the presence of specific antibodies was, with only two exceptions, generally correlated with mRNA expression of the antigen within cell lines derived from the same patient. While cross-reactivity of patients' IgG might play a role in these cases, antibodies from patients' sera were able to distinguish even the closely related MAGE-A3 and -A6. In general, the mRNA expression frequency was higher than the detected IgG responses. Conclusions Antibody recognition of specific tumour antigens by patients' sera may be used for evaluating the possible immunogenicity of new antigens; serological tests could be used for tumour monitoring purposes. [source] Functional roles of immature dendritic cells in impaired immunity of solid tumour and their targeted strategies for provoking tumour immunityCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2006R. Kim Summary Dendritic cells play a crucial role in initiating tumour immunity as well as in the immune response for invading foreign pathogens such as bacteria and viruses. For bacterial and viral infections, the immature dendritic cells (iDCs) residing in peripheral tissues are efficiently activated and matured by pathogen signals for performing the immune response. In contrast, for self-antigens, the naive T cells are not activated by iDCs but proceed to anergy/deletion, and the generation of regulatory T cells for immune tolerance. The induction of immune response and tolerance is regulated strictly by iDCs as the sensor for homeostasis of immune response in the host. Despite the identification of some tumour antigens, tumour immunity is not provoked successfully. Even though there are some critical obstacles to inhibit effective tumour immunity, tumour cells are able to exploit the functional roles of iDCs for tumour progression, which are induced by tumour-derived soluble factors such as vascular endothelial growth factor (VEGF) and functionally modulated in the microenvironment. The iDCs still remain as the critical target for provoking tumour immunity. In this review, the functional roles of tumour-associated iDCs and the strategy for targeting iDCs in effective tumour immunity for the cancer patient are discussed. [source] | ||||||||||