Search results for "Cytolysis"
showing 10 items of 40 documents
Abstract 1138: The protein disulfide isomerase inhibitor XCE853 inhibits in vitro, ex-vivo and in vivo growth of human tumors
2017
Abstract Protein disulfide isomerase (PDI) is a chaperone protein that regulates oxidative protein folding as well as cell viability. Increased PDI levels have been documented in a variety of human cancers associated with a poor overall survival, including ovarian, prostate, brain and lung cancers. Inhibition of PDI activity leads to apoptosis in cancer, suggesting that PDI is a promising druggable target. XCE853 is a synthetic small molecule displaying an excellent docking with the catalytic domain of the human PDI. XCE853 inhibits in vitro recombinant PDI enzymatic activity. In addition, the proliferation of a large panel of human tumor cells is blocked by XCE853 with IC50s in the nanomol…
Analysis of antigens recognized on human melanoma cells by A2-restricted cytolytic t lymphocytes (CTL)
1993
We have pursued our analysis of potential tumor-rejection antigens recognized on human melanoma by autologous cytolytic T lymphocytes (CTL). We reported previously that 3 distinct antigens (A,B,C) were recognized on melanoma cell line SK29-MEL in association with HLA-A2. Selection for melanoma-cell variants resistant to anti-A CTL revealed that antigen A consists of at least 2 determinants (Aa, Ab) which can be lost separately. Genetic linkage between Aa and Ab was suggested by concomitant loss of Aa and Ab in an immunoselected tumor-cell variant. This variant was also resistant to an autologous CTL clone restricted by HLA-B45, indicating that this CTL may also recognize a determinant of an…
Production of stable cytolytic T-cell clones directed against autologous human melanoma
1987
We have attempted to optimize the production of stable human cytolytic T lymphocyte clones directed against autologous melanoma cell lines. MLTC were restimulated every week with irradiated melanoma cells in medium containing human serum and IL-2. After 21 to 35 days, in 5 out of 6 patients, these cultures expressed a preferential cytolytic activity against the autologous melanoma cells, as compared to autologous EBV-B cells or NK target K562. Limiting dilution of MLTC responder cells was performed at times varying from days 7 to 28, in medium containing IL-2 and allogeneic EBV-B cells as feeders. Approximately 1% of these responder cells gave rise to CTL clones that lysed the autologous me…
A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma.
1995
A mutated cyclin-dependent kinase 4 (CDK4) was identified as a tumor-specific antigen recognized by HLA-A2. 1-restricted autologous cytolytic T lymphocytes (CTLs) in a human melanoma. The mutated CDK4 allele was present in autologous cultured melanoma cells and metastasis tissue, but not in the patient's lymphocytes. The mutation, an arginine-to-cysteine exchange at residue 24, was part of the CDK4 peptide recognized by CTLs and prevented binding of the CDK4 inhibitor p16INK4a, but not of p21 or of p27KIP1. The same mutation was found in one additional melanoma among 28 melanomas analyzed. These results suggest that mutation of CDK4 can create a tumor-specific antigen and can disrupt the ce…
T-CELL-MEDIATED CYTOLYSIS : FROM THE LYSIS OF H-2 NEGATIVE TARGET CELLS TO THE INDUCTIVE EFFECT OF XENOGENEIC SERUM
1979
Publisher Summary This chapter describes the results of a series of experiments. In the first series, evidence was found in favor of some specificity of cytolysis against embryonic antigens at the surface of the F9 cells. In a second series of experiments, it was found that P815 and EL4 cells were lysed. From a systematic investigation of the parameters of this system, two facts emerged. F9 cells were not necessary during the in vitro boost incubation. There was some preferential lysis of targets having the same H-2 as the mice receiving the H-2-less F9. For instance, if F9 cells were injected into B1O mice, and after 2–3 weeks, the spleen cells were incubated for 5 days in conventional tis…
Functional Analysis of Alloreactive Helper T Cells Involved in the Induction of Cytolytic T Cell Responses In Vitro
1984
When T-responder cells are sensitized in vitro to foreign antigen presented on syngeneic cells or towards allogeneic stimulator cells, a proliferative response is initiated in which antigen specific cytotoxic T lymphocytes (CTL) are generated. The induction of CTL, however, requires the collaboration between functionally distinct T cell subpopulations1–5 and accessory cells from the macrophage lineage, including dendritic cells. The experimental data accumulated so far reveal a cascade of T-T cell interactions and distinct functions of their soluble products resulting in the “Interleukin concept”6 (Fig. 1). Upon receptor-antigen interaction, the “antigen-selected” clones of CTLp become sens…
Alloreactive and H-2-restricted Lyt 23 cytotoxic T lymphocytes derive from a common pool of antecedent Lyt 123 precursors.
1980
If the collaborative requirement of Lyt 1 T helper cells is bypassed by the Lyt 1 T cell-derived mediator of T help, termed Il-2, upon antigenic stimulation, PNA+ Lyt 123 thymocytes differentiate into either alloreactive or H-2-restricted PNA- Lyt 23 cytotoxic effector cells. Along the differentiation pathway from Lyt 123 leads to 23 effector cells, cytolytic activity is carried out by T cells that still express the Lyt 123 phenotype. The data establish that Lyt 23 CTL are produced by differentiation from antecedent Lyt 123 cells.
Virion Antigens Introduced Exogeneously into the Cell Membrane Render Syngeneic Target Cells Susceptible for T Cell-Mediated Cytolysis
1977
Non-infectious sendai virus renders H-2 matched target cells susceptible to the lytic effect of sendai virus immune cytotoxic T lymphocytes. This observation suggests that exogeneous insertion of virion antigen in the membrane of the target cell is sufficient for T cell cytotoxicity. The finding is incompatible with the concept that H-2K or H-2D gene products of the target cells must be altered in their primary structure (pretranslational effect of the virus infection) for T cell-mediated cytolysis to occur.
Fine specificity and cytolytic activity of continuously growing alloreactive cytotoxic T lymphocyte clones.
1980
The role of Lyt 1+ T-cell-derived secondard CTL inducing factor allowed the cloning of alloreactive cytotoxic T lymphocytes (CTL) by the limiting dilution approach. Several monoclonal cell lines were established in vitro. The lytic activity of some of the cell lines exceeded that of CTL from bulk cultures; that is, 50% of the target cells were lysed at an effector to target cell ratio of 0.04:1. The fine specificity of individual CTL clones is discussed.
Herpes-Simplex-virus-specific, H-2Dk-restricted T lymphocytes bear receptors for H-2Dd alloantigen.
1980
Cytotoxic T lymphocytes generated in the course of an HSV-infection of CBA (H-2k) mice not only lyse syngeneic, virus-infected target cells but also cross-react with noninfected taraget cells expressing the Dd alloantigen. On the effector cell level, this alloreactivity is mediated by virus-specific CTL's that are restricted to H-2Dk determinants. On the prekiller cell level, the anti-HSV-reactive T cells exhibiting cross-reactivity for Dd alloantigen could be positively selected on H-2d spleen-cell monolayers. After differentiation into cytolytic effector cells, target cells expressing Dd alloantigens and syngeneic HSV-infected target were lysed with equal efficiency. The results imply tha…