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Liposome encapsulated tumor-associated antigens elicited humoral and cellular immune responses in mice bearing tumor 总被引:1,自引:0,他引:1
Chemically induced tumors in mice provide a system to investigate tumor-associated antigens (TAA). The cell surface glycoprotein antigens on such tumor cells have been identified as suitable targets for immune attack. The induction of immune responses against (TAA) in N-nitrosodiethylamine (DEN) exposed mice has been examined. In order to present antigens to the immune system, the liposome was used as vehicle to deliver the TAA. Liposomal-TAA formulation, elicited both humoral and the cellular immune responses, when administered intramuscularly in DEN-exposed mice. Presence of circulatory antibodies against TAA and the induction of cellular responses in immunized mice were monitored using ELISA and in vitro cell proliferation assay of lymphocytes respectively. Specificity of antibody against TAA in immune sera was analysed using immunoblotting technique. Based on these results, it is proposed that the liposome encapsulated TAA may successfully be used to induce humoral and cellular immune responses against tumor. 相似文献
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Pulido J Kottke T Thompson J Galivo F Wongthida P Diaz RM Rommelfanger D Ilett E Pease L Pandha H Harrington K Selby P Melcher A Vile R 《Nature biotechnology》2012,30(4):337-343
Multiple intravenous injections of a cDNA library, derived from human melanoma cell lines and expressed using the highly immunogenic vector vesicular stomatitis virus (VSV), cured mice with established melanoma tumors. Successful tumor eradication was associated with the ability of mouse lymphoid cells to mount a tumor-specific CD4(+) interleukin (IL)-17 recall response in vitro. We used this characteristic IL-17 response to screen the VSV-cDNA library and identified three different VSV-cDNA virus clones that, when used in combination but not alone, achieved the same efficacy against tumors as the complete parental virus library. VSV-expressed cDNA libraries can therefore be used to identify tumor rejection antigens that can cooperate to induce anti-tumor responses. This technology should be applicable to antigen discovery for other cancers, as well as for other diseases in which immune reactivity against more than one target antigen contributes to disease pathology. 相似文献
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Shebzukhov IuV Belousov PV Khlgatian SV Sazykin AIu Kuprash DV Nedospasov SA 《Molekuliarnaia genetika, mikrobiologiia i virusologiia》2007,(2):3-6
Humoral immune response to tumor-associated antigens in cancer patients can be used as a basis for disease diagnosis and monitoring. Moreover, identification of molecular targets of such response may be used to develop antigen-specific anticancer vaccines. Here, we review the main approaches to identification and study of tumor-associated antigens recognized by serum antibodies. We also focus on the challenges that must be met before serological antigens can be used in clinical cancer diagnostics. 相似文献
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Miriam Reuschenbach Magnus von Knebel Doeberitz Nicolas Wentzensen 《Cancer immunology, immunotherapy : CII》2009,58(10):1535-1544
This review summarizes studies on humoral immune responses against tumor-associated antigens (TAAs) with a focus on antibody
frequencies and the potential diagnostic, prognostic, and etiologic relevance of antibodies against TAAs. We performed a systematic
literature search in Medline and identified 3,619 articles on humoral immune responses and TAAs. In 145 studies, meeting the
inclusion criteria, humoral immune responses in cancer patients have been analyzed against over 100 different TAAs. The most
frequently analyzed antigens were p53, MUC1, NY-ESO-1, c-myc, survivin, p62, cyclin B1, and Her2/neu. Antibodies against these TAAs were detected in 0–69% (median 14%) of analyzed tumor patients. Antibody frequencies were
generally very low in healthy individuals, with the exception of few TAAs, especially MUC1. For several TAAs, including p53,
Her2/neu, and NY-ESO-1, higher antibody frequencies were reported when tumors expressed the respective TAA. Antibodies against
MUC1 were associated with a favorable prognosis while antibodies against p53 were associated with poor disease outcome. These
data suggest different functional roles of endogenous antibodies against TAAs. Although data on prediagnostic antibody levels
are scarce and antibody frequencies for most TAAs are at levels precluding use in diagnostic assays for cancer early detection,
there is some promising data on achieving higher sensitivity for cancer detection using panels of TAAs.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
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A. Quintanar-Stephano E. Abarca-Rojano R. A. Jarillo-Luna V. Rivera-Aguilar J. Ventura-Juárez I. Berczi K. Kovacs R. Campos-Rodríguez 《Journal of physiology and biochemistry》2010,66(1):7-13
In rats, hypophysectomy (HYPOX) or neurointermediate pituitary lobectomy (NIL) reduce humoral and cell-mediated immune responses.
However, to our knowledge, the differences in the effects of anterior versus posterior pituitary hormones on the immune responses
have not been studied to date. We compared in rats, the effects of sham surgery (SHAM), HYPOX, and NIL on humoral immune responses
to T cell-independent (TI) type 1 antigen DNP-LPS and to TI type 2 antigen DNP-FICOLL, as well as to T cell-dependent (TD)
antigens ovalbumin (OVA) and bovine serum albumin (BSA). The results showed that: (1) both HYPOX and NIL induced a similar
and significant decrease in IgM responses towards TI-1 antigens, (2) NIL but not HYPOX induced a decreased IgM response to
TI-2 antigens, and (3) both HYPOX and NIL induced similar and significant decrease in IgG responses to TI-2 antigens. Compared
with the SHAM group, IgM responses to both TD antigens did not change in HYPOX and NIL animals, whereas the IgG responses
to OVA and BSA significantly decreased in HYPOX and NIL animals. These results indicate that hormones of the anterior and
posterior pituitary play their own role in the regulation of humoral immune responses. 相似文献
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J C Bystryn 《Journal of immunology (Baltimore, Md. : 1950)》1976,116(5):1302-1305
Synthesis and release of radiolabeled macromolecules and tumor-associated antigens (MAA) by murine B16 melanoma was studied by pulse labeling cells in culture with 3H-leucine. Approximately 36% of newly synthesized macromolecules and 44% of newly synthesized MAA were released in 48 hr. MAA release was slightly, but consistently, more rapid than the average release of other macromolecules. Release of MAA did not result solely from cell death since it was greater than that of 51Cr-labeled molecules and cell viability was over 98%. The rate of release of newly synthesized MAA was not significantly influenced by cell replication. However, synthesis of MAA was much greater during the logarithmic than the stationary phase of cell growth, suggesting a concomitant increase in the amount of MAA available for release. These findings indicate that antigens and other macromolecules can be rapidly released by viable tumor cells. 相似文献
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D Chao S R Wong H T Ng 《Proceedings of the National Science Council, Republic of China. Part B, Life sciences》1989,13(3):171-175
The occurrence of immunosuppression in mice inoculated with antigens prepared from Trichomonas vaginalis was investigated in this study. One hundred and fourteen BALB/c mice with half of each sex were divided into 19 groups and inoculated with different antigen preparations before or after sheep red blood cell (Srbc) immunization. Antigen preparations included live T. vaginalis (LTV), excretory and secretory products (ESP), and freeze and thaw antigens (FTA). The immunosuppressive effects of these T. vaginalis-derived antigens were demonstrated by the decrease of hemagglutination titers to Srbc. Results indicated that all three antigen preparations exhibited immunodepressive potentials in the primary and secondary responses to Srbc. Among them, FTA showed the highest inhibitory effect. The duration of the effect persisted for 21 days. The immunosuppressive effect was not observed for antigens which were given after Srbc injection. 相似文献
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Summary A suppressive immunoregulatory factor (IRF) produced by murine melanoma K-1735 M3 has been identified. Extracts from tissue or cultured cells grown in serummedium were prepared by 3 M KCl extraction and partially purified by low-salt precipitation. IRF extracted from fresh tumor, cultured cells, and spent medium from the K-1735 cell line suppressed 3H-thymidine incorporation by splenocytes during mitogen stimulation. Cell viability was not impaired by IRF. IRF suppressed splenocyte proliferation, protein synthesis, murine IL-2-mediated blastogenesis, and mixed splenocyte responses. However, in vitro generation of allogenic cytotoxic cells was not suppressed. Significant inhibitory activity could not be extracted from normal tissues. IRF activity was reduced by treatment with proteolytic enzymes and neuraminidase and was bound by lentil lectin, indicating that the factor is a glycoprotein. IRF was heat-stable, yet labile to treatment with acid, base, or 2-mercaptoethanol. Inhibitory activity was partially characterized by preparative isoelectric focusing (pI 3.5–5.8), and the active moiety had a molecular size of 10–12 K according to HPLC. The HPLC-purified active fraction of IRF did not contain the immunosuppressive retroviral antigen p15(E). Splenocytes from animals treated with IRF in vivo demonstrated reduced responses to Con A and PHA in vitro. Suppressor cells were not identified. We have identified a low-molecular-weight glycoprotein from a murine melanoma, which suppresses a variety of immunologic responses in vitro and in vivo. IRF appears to be a potent mediator of tumor-induced immunosuppression in this model.Abbreviations ACK
ammonium chloride-potassium erythrocyte lysing buffer
- BSA
bovine serum albumin
- CM
complete medium
- Con A
concanavalin A
- HBSS
Hank's balanced salt solution
- HPLC
high-performance liquid chromatography
- HS
hepes sucrose
- IL-2
interleukin II (lectin-free)
- IRF
immunoregulatory factor
- Leu
L-leucine
- LPS
lipopolysaccharide
- M3
metastasis from murine melanoma K-1735
- MASH
multiple automated sample harvester
- PBS
phosphate-buffered saline
- PIEF
preparative isoelectric focusing
- PHA
phytohemaglutinin
- PWM
pokeweed mitogen
- Tdr
thymidine 相似文献
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K Imai A K Ng M C Glassy S Ferrone 《Journal of immunology (Baltimore, Md. : 1950)》1981,127(2):505-509
Incubation of cultured human melanoma cells with human leukocyte interferon did not change the expression of melanoma-associated antigens (MAA) recognized by monoclonal antibodies and of Ia-like antigens but significantly increased the expression of HLA-A,B antigens and of beta 2-microglobulin (beta 2-mu). The effect is dependent on the dose of interferon and on the incubation time. Interferon-treated melanoma cells showed an increased susceptibility to lysis mediated by monoclonal antibodies to HLA-A,B antigens and to human beta 2-mu; on the other hand, interferon-treated melanoma cells did not change in their susceptibility to murine natural killer (NK) cell lysis and to immune lysis mediated by monoclonal antibodies to MAA and to Ia-like antigens, and they displayed a reduced susceptibility to human NK cell lysis. Therefore, the increased susceptibility of interferon-treated melanoma cells to lysis mediated by anti HLA-A,B and anti beta 2-mu monoclonal antibodies is likely to reflect the increase in cell surface expression of the corresponding antigens. 相似文献
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D Hannani C Locher T Yamazaki V Colin-Minard M Vetizou L Aymeric S Viaud D Sanchez M J Smyth P Bruhns G Kroemer L Zitvogel 《Cell death and differentiation》2014,21(1):50-58
Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4+ and CD8+ T cells producing interferon-γ. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-cell-depleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas. 相似文献
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Transcriptional regulation of Fcgr2b gene by polymorphic promoter region and its contribution to humoral immune responses 总被引:4,自引:0,他引:4
Xiu Y Nakamura K Abe M Li N Wen XS Jiang Y Zhang D Tsurui H Matsuoka S Hamano Y Fujii H Ono M Takai T Shimokawa T Ra C Shirai T Hirose S 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(8):4340-4346
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Dimethyldioctadecylammonium bromide (DDA) produced marked enhancement of both cellular and humoral immune responses to SRBC when administered to mice intraperitoneally, or of cellular immunity when given subcutaneously. Stimulated cellular responses were seen as increased footpad swelling as a measure of delayed hypersensitivity and increased antigen-induced blastogenesis. Elevation of humoral response was reflected in increased numbers of splenic plaque-forming cells (PFC) and in circulating anti-SRBC antibody. Adjuvancy did not depend on addition of the lipid of DDA to antigen, as both humoral and cellular responses were enhanced whether DDA and SRBC were admixed or injected separately 4 hr apart intraperitoneally. DDA also enhanced the PFC response to the T-cell independent antigen TNP-LPS. The DDA effects are accompanied by macrophage activation, which may mediate at least in part the observed responses. DDA-activated macrophages exhibit fast spreading, are highly phagocytic, and elaborate significantly greater amounts of thymocyte mitogenic factor(s) than do normal resident peritoneal macrophages. This activation may effect the stimulation of antigen-specific primary lymphocyte responses by adjuvant and expansion of memory-cell populations which lead to the observed enhancement of secondary responses. 相似文献
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Recombinant proteins of the RH strain of Toxoplasma gondii were produced by expression in Escherichia coli as glutathione S-transferase (GST) fusion proteins. Enzyme-linked immunosorbent assays were established using 2 of these fusion proteins termed H4/GST and H11/GST. The assays were able to detect antibodies in the sera of mice orally infected with either the cyst or oocyst stage of a pork isolate of T. gondii. In addition, the sera from mice infected with 1 of 4 different T. gondii isolates were investigated for their binding to these fusion proteins. Antibodies in the sera of all mice bound to H11/GST, but not all sera recognized H4/GST. Delayed-type hypersensitivity (DTH) responses to the fusion proteins were found when the mice were sensitized intradermally with H4/GST and H11/GST and challenged with the homologous fusion protein. However, no DTH response was recorded when mice were challenged with homologous fusion proteins after infection with T. gondii, or after immunization with a sonicate of the RH strain of the parasite. In addition, cellular responses were not stimulated against either of the fusion proteins in in vitro assays. These 2 fusion proteins were recognized by anti-T. gondii antibodies in experimental murine infections, and they are therefore potential candidates as antigens in assays for the diagnosis of human toxoplasmosis. 相似文献
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Spontaneous T cell responses to melanoma differentiation antigens from melanoma patients and healthy subjects 总被引:2,自引:0,他引:2
Qiyuan Chen Heather Jackson Peter Gibbs Ian D. Davis Joseph Trapani Jonathan Cebon 《Cancer immunology, immunotherapy : CII》1998,47(4):191-197
The spontaneous cytotoxic T cell responses to melanoma differentiation antigens and influenza matrix peptide were compared
in 20 HLA-A2+ melanoma patients and 17 healthy A2+ individuals. Cytotoxic T lymphocyte (CTL) responses were determined by mixed lymphocyte peptide culture (MLPC) involving
two stimulations of unfractionated peripheral blood lymphocytes (PBLs) with peptide in vitro. CTL responses to Melan-A 9-mer
(amino acids 27–35, AAGIGILTV) peptide were detected in 4 out of 16 normal individuals, but in none of the melanoma patients.
CTL specific for influenza matrix peptide were frequently found in both normal individuals and melanoma patients, suggesting
that generalized immuno-suppression was not responsible for this difference. No significant responses were observed in either
normal individuals or melanoma patients to Melan-A 10-mer (26–35, EAAGIGILTV), two gp100 epitopes (280–288, YLEPGPVTA; 457–466,
LLDGTATLRL) and two tyrosinase epitopes (1–9, MLLAVLYCL; 368–376, YMDGMSQV). Melan-A (27–35)-specific CTL cells generated
by normal individuals and melanoma patients recognized both synthetic peptide-pulsed T2 cells and two HLA-A2+, Melan-A+ melanoma cell lines (ME272, LAR1) in an antigen-specific, MHC class I restricted manner. T cells generated against Melan-A
9-mer were also able to recognize Melan-A 10-mer-pulsed target cells. Spontaneous CTL responses to Melan-A 9-mer from three
known responder normal individuals were further evaluated over a prolonged time course (6–11 months). All 3 subjects demonstrated
specific Melan-A 9-mer responses throughout the study period, although lytic activity fluctuated over time for a given individual.
We found the MLPC assay to be reliable and easy to perform for monitoring T cell responses, although it may still not be sufficiently
sensitive to detect low numbers of precursor T cells.
Received: 21 May 1998 / Accepted: 23 July 1998 相似文献
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Immunostimulant adjuvant patch enhances humoral and cellular immune responses to DNA immunization 总被引:1,自引:0,他引:1
Mkrtichyan M Ghochikyan A Movsesyan N Karapetyan A Begoyan G Yu J Glenn GM Ross TM Agadjanyan MG Cribbs DH 《DNA and cell biology》2008,27(1):19-24
The focus of this report is on the development of an improved DNA immunization protocol, which takes advantage of the strengths of DNA immunization, as well as those associated with adjuvant delivered by transcutaneous immunostimulatory (IS) patches. Because transcutaneous delivery of adjuvants to the skin at the vaccination site has been shown to amplify the immune response to protein antigens, we hypothesized that the same IS patch when placed on the skin at the site of DNA injection could further enhance the immune response to a DNA influenza vaccine. We have combined an influenza DNA vaccine, hemagglutinin fused with three copies of complement C3d, to enhance uptake and antigen presentation, with an IS patch containing heat-labile enterotoxin from Escherichia coli. Coadministration of a potent adjuvant in IS patches placed on the skin at the site of DNA vaccination dramatically amplifies anti-influenza antibody immune response. Supplementing DNA vaccines with IS patches may be a particularly valuable strategy because DNA vaccines can be rapidly modified in response to mutations in pathogens, and individuals with compromised immune systems such as transplant patients and the elderly will benefit from the enhanced antibody response induced by the IS patches. 相似文献