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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mice carrying large established major histocompatibility complex (MHC) class 1+ sarcoma tumors can be successfully treated by immunization with genetically engineered sarcoma cells transfected with syngeneic MHC class II plus B7-1 genes. This approach is significantly more effective than previously described strategies using cytokine- or B7-transduced tumor cells which are only effective against smaller tumor loads, and which cannot mediate regression of longer-term established tumors. The most efficient tumor rejection occurs if both the class II and B7-1 molecules are coexpressed on the same tumor cell. Immunity induced by immunization with class II+B7-1(+)-transfected sarcoma cells involves CD4+ and CD8+ T cells, suggesting that the increased effectiveness of the transfectants is due to their ability to activate both of these T cell populations.
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PMID:Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice. 783 17

The growth pattern (progression/regression) of v-src DNA- and Rous sarcoma virus (RSV)-induced tumors was analogous on a panel of inbred chicken lines. The decisive role of the major histocompatibility complex [Mhc(B)] alleles in resistance to the progression of these tumors was formally proved in segregating backcross populations. The immune mechanism of tumor regression was demonstrated by both in vivo and in vitro assays. A protective effect of v-src-specific immunity against RSV challenge was shown in Rous sarcoma regressor, line CB (B12/B12). Immune cells from regressors of v-src DNA-induced tumors can protect syngeneic hosts from the development of tumor after challenge with both v-src DNA and RSV. Suppression of RSV-induced tumor cell growth in vitro was also achieved by the use of cocultivation with spleen cells from chickens in which v-src DNA-induced tumors had regressed. This in vitro sarcoma-specific response was Mhc(B)-restricted. Chickens of the congenic Rous sarcoma progressor line CC (B4/B4) are sometimes able to regress v-src DNA-induced tumors, but immune cells can only slow the growth of v-src DNA-induced tumors in syngeneic hosts. This suggests that the primary reason for the susceptibility of CC chickens is a weak v-src-specific immune response. Furthermore, some of the v-src DNA-induced tumors were transplantable across the Mhc(B) barrier. The growth of tumor allografts was able to be facilitated when immunological tolerance to the B-F/L region antigens (class I and class II) had been established. This demonstrated that a high tumorigenicity of the transplantable tumor was not due to the lack of Mhc(B) antigens on tumor cells.
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PMID:src-specific immunity in inbred chickens bearing v-src DNA- and RSV-induced tumors. 808 91

Sensitized peripheral blood lymphocytes (PBL) obtained from canine transmissible venereal sarcoma (CTVS)-regressed dogs were more cytotoxic against CTVS cells than non-sensitized PBL from untreated dogs. Cytotoxicity shown by sensitized PBL was inhibited significantly by the addition of anti-major histocompatibility complex (MHC) class II mouse monoclonal antibody as well as that of anti-dog thymocyte rabbit serum. The degree of cytotoxic activity shown by lymphokine activated killer (LAK) cells induced from non-sensitized or sensitized PBL was similar to that of the activity shown by sensitized PBL. These LAK activities were also prohibited by the addition of anti-dog thymocyte rabbit serum. Immunohistochemical examination demonstrated that MHC class II antigens were expressed on the surface membrane of CTVS cells and thymocyte antigens were detected on the surface of the tumor infiltrating lymphocytes. From the results mentioned above, lymphocytes which play a central role in tumor regression are considered to be T cells. These cells might recognize MHC class II antigens on the surface membrane of CTVS cells in tumor regression.
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PMID:Role of lymphocytes in spontaneous regression of experimentally transplanted canine transmissible venereal sarcoma. 820 42

In previous studies we have shown that the highly malignant mouse SaI sarcoma can be converted into an immunogenic tumor that is immunologically rejected by the autologous host if the tumor cells are transfected with and express syngeneic major histocompatibility complex (MHC) class II genes. Tumor cells expressing class II heterodimers truncated for the cytoplasmic regions of the alpha and beta chains, however, are as malignant as wild-type class II- tumors. These studies have contributed to the hypothesis that T-cell activation requires two signals: the engagement of the MHC class II/peptide complex of the antigen-presenting cell (APC) by the T cell receptor for antigen of the responding T cell and the transmittal of a second, or costimulatory, signal by the APC to the responding T cell. In this report we show that induction of tumor-specific immunity is facilitated by delivery of a costimulatory signal provided by the B7 activation molecule. Mice challenged with SaI cells bearing truncated class II molecules and transfected with B7 cDNA are immune to the transfectants and are protected against a challenge of wild-type class II-B7- ascites or solid SaI tumor. The induced immunity requires CD4+ T cells and is specific for the immunizing sarcoma cells. These results highlight the critical role of the B7 costimulatory pathway in stimulating long-term, tumor-specific immunity that is effective against high doses of challenging wild-type tumor and suggest a strategy for enhancing tumor rejection.
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PMID:Tumor cells expressing major histocompatibility complex class II and B7 activation molecules stimulate potent tumor-specific immunity. 829 2

Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector MFG-granulocyte-macrophage colony-stimulating factor (GM-CSF), to examine immune stimulation conferred by localized GM-CSF production. Expression of murine GM-CSF by neuro-2a (N-2a/GM) significantly reduced its tumorigenicity. Moreover, immunization of mice with irradiated N-2a/GM cells resulted in a significant protective effect against live tumor challenge 14 days later. Approximately 41% of mice immunized with irradiated N-2a/GM versus 0% of those vaccinated with irradiated parental tumor survived. Surviving mice were rechallenged after 50 days with wild-type neuro-2a or with the Sa1 syngeneic sarcoma to discern whether the generated immunity was durable and tumor specific. All mice survived wild-type neuro-2a challenge, whereas none survived inoculation with Sa1. Because both CD4+ and CD8+ T cells were necessary during priming to this MHC class Ilo, II-tumor, these data indicate that major histocompatibility complex (MHC) class I+, II+ antigen-presenting cells (APCs) were required for the T-cell antitumor response. Co-expression of GM-CSF and IFN-gamma, both of which have immunostimulatory activities on antigen-presenting cells, abrogated the tumorigenic potential of this tumor and increased immunogenicity over N-2a/IFN but not N-2a/GM. Vaccination of mice with preexisting retroperitoneal tumors with irradiated N-2a/GM and irradiated N-2a/IFN/GM improved survival. There was a trend for nonirradiated transduced cells to be more immunogenic than their irradiated counterparts. Immunohistochemistry of tissues from the vaccination site revealed a pronounced macrophage infiltration associated with nonirradiated N-2a/GM and N-2a/IFN/GM. These data suggest that vaccination involving nonirradiated neuroblastoma cells transduced with genes that stimulate APCs may be a useful approach in stimulating antitumor T-cell responses.
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PMID:Effective immunization against neuroblastoma using double-transduced tumor cells secreting GM-CSF and interferon-gamma. 873 94

Immune surveillance against tumors usually depends on T cell recognition of tumor antigens presented by major histocompatibility complex (MHC) molecules, whereas MHC class I- tumors may be controlled by natural killer (NK) cells. Perforin-dependent cytotoxicity is a major effector function of CD8+ MHC class I-restricted T cells and of NK cells. Here, we used perforin-deficient C57BL/6 (PKO) mice to study involvement of perforin and Fas ligand in tumor surveillance in vivo. We induced tumors in PKO and normal C57BL/6 mice by (a) injection of different syngeneic tumor cell lines of different tissue origin in naive and primed mice; (b) administration of the chemical carcinogens methylcholanthrene (MCA) or 12-O-tetradecanoylphorbol-13-acetate (TPA) plus 7,12-dimethylbenzanthracene (DMBA), or (c) by injection of acutely oncogenic Moloney sarcoma virus. The first set of models analyzes the defense against a tumor load given at once, whereas the last two sets give information on immune defense against tumors at the very moment of their generation. Most of the tumor cell lines tested were eliminated 10-100-fold better by C57BL/6 mice in an unprimed situation; after priming, the differences were more pronounced. Lymphoma cells transfected with Fas were controlled 10-fold better by PKO and C57BL/6 mice when compared to untransfected control cells, indicating some role for FasL in tumor control. MCA-induced tumors arose more rapidly and with a higher incidence in PKO mice compared to C57BL/6 or CD8-deficient mice. DMBA+TPA-induced skin papillomas arose with similar high incidence and comparable kinetics in both mouse strains. C57BL/6 and PKO mice have a similar incidence of Moloney murine sarcoma and leukemia virus-induced sarcomas, but tumors are larger and regression is retarded in PKO mice. Thus, perforin-dependent cytotoxicity is not only a crucial mechanism of both cytotoxic T lymphocyte- and NK-dependent resistance to injected tumor cell lines, but also operates during viral and chemical carcinogenesis in vivo. Experiments addressing the role of Fas-dependent cytotoxicity by studying resistance to tumor cell lines that were stably transfected with Fas neither provided evidence for a major role of Fas nor excluded a minor contribution of Fas in tumor surveillance.
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PMID:Decreased tumor surveillance in perforin-deficient mice. 892 Aug 66

Following non-lethal heat stress (41.8 degrees C) and a recovery period at 37 degrees C, the inducible 72kDa HSP (HSP72) is detectable selectively on the cell surface of human Ewing's Sarcoma (ES) and of leukemic K562 cells but not on EBV transformed B cells (B-LCL) which were generated from PBL of healthy human volunteers. The HSP72 expression was measured by flowcytometric analysis using a monoclonal antibody (moAb) that specifically recognizes HSP72, the inducible form of the HSP70 group. The major histocompatibility complex (MHC) class I expression, detected with moAb W5/32 was not affected by non-lethal heat exposure and a recovery period at 37 degrees C for 12 h: ES cells express MHC class I molecules on about 80% of the cells; K562 cells exhibited no MHC class I expression neither before nor after heat shock. Inhibition of RNA-(actinomycin D) of protein-synthesis (cycloheximide) prior to heat treatment completely inhibits the expression of HSP72 on the cell surface of both tumour cells, thus indicating that de novo protein synthesis is required for HSP72 cell surface expression. Since, apart from HSP72, protein synthesis in general is down-modulated by heat shock we speculate that HSP72 molecules that are expressed on the cell surface of tumour cells might be recruited from newly synthesized proteins. The heat-inducible HSP72 cell surface expression on tumour cells could be correlated with an increased sensitivity of leukemic and sarcoma cells to lysis mediated by NK effector cells. The results of cold target inhibition assays revealed that histologically different tumour cells (sarcoma and leukemic cells) that were exposed to non-lethal temperatures have to share a similar if not identical HSP72 immunogenic determinant.
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PMID:Heat shock protein 72 (HSP72), a hyperthermia-inducible immunogenic determinant on leukemic K562 and Ewing's sarcoma cells. 902 25

We have developed an immunotherapy in which tumor cells transfected with syngeneic major histocompatibility complex (MHC) class II genes are cell-based vaccines for the treatment of established tumor and metastatic disease. If this strategy is to be used clinically, convenient methods for generating class II+ tumor cells are necessary. Interferon-gamma treatment or transduction of the class II transactivator (CIITA) gene induces class II expression but also up-regulates the class II-associated accessory molecules, invariant chain (Ii) and DM. To determine if interferon-gamma treatment and CIITA transduction are potential immunotherapies, we assessed the tumorigenicity of sarcoma cells expressing combinations of class II, Ii, and DM. Since we hypothesized that class II-transfected tumor cells not coexpressing Ii and DM present endogenously encoded tumor peptides, we have assessed the transfectants for antigen presentation activity to MHC class II-restricted antigen-specific CD4(+) T cells. Tumor challenge studies demonstrate that tumor cells expressing class II without coexpression of Ii or Ii plus DM are highly immunogenic and preferentially present endogenous antigens, while tumors coexpressing class II with Ii or Ii plus DM are not effective immunogens. Because tumor rejection correlates with expression of class II without coexpression of Ii and DM, the most efficacious vaccines will express MHC class II without coexpression of Ii and DM and will preferentially present endogenous antigen.
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PMID:Major histocompatibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of tumor-specific immunity. 919 61

Seventy-eight uncloned tumour cell lines, each established from a primary sarcoma induced with methyl-cholanthrene in immunocompetent nu/+ BALB/c and C.B.-17 mice or in immunodeficient nu/nu BALB/c and severe combined immunodeficient (SCID) mice, were examined for sensitivity to interferon-gamma (IFN-gamma) as measured by tumour cell augmentation of major histocompatibility complex (MHC) class I expression. The tumour cells were cultured with IFN-gamma and their expression of Kd, Dd and Ld was measured by fluorescence-activated cell sorter analysis. All but three of the 78 tumour lines up-regulated Kd, Dd and Ld to a variable degree in response to IFN-gamma, indicating that IFN-gamma resistance is not a common property of these sarcomas. The tumour cell lines varied greatly in their MHC class I expression before as well as after IFN-gamma stimulation. There was a tendency towards a higher MHC expression after IFN-gamma stimulation in tumour lines from immunocompetent mice compared to immunodeficient mice, but no common maximum MHC class I expression level was found for the 78 tumour cell lines. Three of the tumour lines, all from immunodeficient mice, completely failed to respond to IFN-gamma by up-regulating MHC class I expression. The same three also displayed absence of IFN-gamma-induced Stat1 beta tyrosine phosphorylation and low Stat1 alpha tyrosine phosphorylation, indicating a defect in the signal transduction pathway affecting phosphorylation of Stat1. These findings strongly suggest a link between defects in Stat1 phosphorylation and the failure to up-regulate MHC class I. In all tumour lines tested, the Stat1 Western blotting revealed a 78 kDa protein (p78) not previously described.
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PMID:Interferon-gamma-induced MHC class I expression and defects in Jak/Stat signalling in methylcholanthrene-induced sarcomas. 935 Feb 89

The clinical application of synthetic tumor peptide-based vaccines is currently limited to patients with specified major histocompatibility complex (MHC) class I alleles. Such logistic limitations may be overcome using tumor gene-based approaches. Here we describe the effective generation of dendritic cells (DC) expressing tumor peptide-MHC complexes as a result of particle-mediated transfer of genes encoding tumor-associated antigens (TAA). Bone marrow-derived DC were transfected with plasmid DNA encoding the tumor-associated viral antigen E7 derived from human papilloma virus (HPV) 16. When applied as a vaccine, these genetically modified DC induced antigen-specific CD8+ cytotoxic T lymphocytes (CTL) in vivo and promoted the rejection of a subsequent, normally lethal challenge with an HPV 16-transformed tumor cell line. Of greatest interest, immunization of mice with syngeneic DC genetically modified to enhance their presentation of a constitutive "self" epitope derived from the tumor-suppressor gene product p53 caused a significant reduction in the in vivo growth of a chemically induced p53-positive sarcoma. These results suggest that cancer vaccines consisting of DC genetically modified to express TAA of viral or "self" origin effectively induce antitumor immunity in vivo.
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PMID:Genetically modified bone marrow-derived dendritic cells expressing tumor-associated viral or "self" antigens induce antitumor immunity in vivo. 936 29


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