scholarly journals Induction of tumor-specific T cell response by cognating tumor cells with foreign antigen-primed Th cells

1998 ◽  
Vol 10 (10) ◽  
pp. 1397-1406 ◽  
Author(s):  
T. Cheng
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Cell Response ◽  
T Cell Response ◽  
Th Cells ◽  
Foreign Antigen

scholarly journals Concomitant Targeting of Tumor Cells and Induction of T-cell Response Synergizes to Effectively Inhibit Trastuzumab-Resistant Breast Cancer

2012 ◽  
Vol 72 (17) ◽  
pp. 4417-4428 ◽  
Author(s):  
Qingfei Wang ◽  
Shau-Hsuan Li ◽  
Hai Wang ◽  
Yi Xiao ◽  
Ozgur Sahin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Tumor Cells ◽  
Cell Response ◽  
T Cell Response

scholarly journals H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway.

1982 ◽  
Vol 156 (3) ◽  
pp. 822-833 ◽  
Author(s):  
C N Baxevanis ◽  
N Ishii ◽  
Z A Nagy ◽  
J Klein
Keyword(s):  
Lactate Dehydrogenase ◽  
T Cell ◽  
Cell Response ◽  
Cell Types ◽  
T Cell Response ◽  
T Helper ◽  
Th Cells ◽  
Th Cell ◽  
Antigen Presenting

We characterized the cell types involved in the H-2-controlled suppression of T cell response to lactate dehydrogenase B (LDHB). The suppressor effector (Tse) was found to be an Lyt-1+2+, J+ cell that recognizes antigen together with Ek molecules of antigen-presenting cells (APC). To become functional, the Tse cell requires a second signal from a nonspecific, Lyt-1+2-, J+ suppressor-inducer (Tsi) cell. The Tsi-Tse interaction is not subject to any genetic restriction. The target cell of suppression is an Lyt-1+2-, J- (most likely T helper [Th]) cell that recognizes LDHB in the context of A molecules on APC. The suppression is manifested in inhibition of the antigen-specific, A-restricted proliferation of Th cells. The interaction between Tse and Th is restricted by the A region of the H-2 complex. Because this restriction is determined by the receptor of Th cells, the mechanism of Th-Tse interaction most likely involves a concomitant recognition of LDHB and A region-controlled molecules by Th cells on the surface of Tse cells.

Impact of Regulatory T Cells on Antigen Specific T Cell Response Using Recombinant Chimeric T Cell Receptors In Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5475-5475
Author(s):  
David M. Kofler ◽  
Markus Chmielewski ◽  
Heike Koehler ◽  
Tobias Riet ◽  
Patrick Schmidt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
T Cell Receptors ◽  
Cell Response ◽  
Effector T Cells ◽  
T Cell Response ◽  
Cell Receptors

Abstract Recombinant T cell receptors with defined specificity against tumor cells are a promising experimental approach in the elimination of residual leukemia and lymphoma cells. It is so far unresolved whether regulatory T cells with suppressor activities impair the efficiency of cytolytic T cells grafted with a recombinant immunoreceptor. The frequency of regulatory T cells is highly increased in tumor patients and their suppressive function seems to play a role in the fail of an autologous T cell response against the malignant cells. In this study we analyzed the antigen-triggered, specific activation of receptor grafted T cells in the presence or absence of regulatory CD4+CD25high T cells. CD3+ T cells were grafted with CEA-specific immunoreceptors containing the CD3-zeta signaling domain for T cell activation. Co-cultivation of receptor grafted effector T cells together with regulatory T cells repressed proliferation of the effector cells and decreased IL-2 secretion. Secretion of IFN-gamma and IL-10 was not impaired. Interestingly, the cytotoxicity of grafted effector T cells towards CEA-expressing tumor cells was not impaired by regulatory T cells in vitro. To evaluate the relevance in vivo, we used a Crl:CD1 Nu/Nu mouse model to assess growth of CEA+ tumor cells in the presence of receptor grafted effector T cells and of regulatory T cells. Mice inoculated with tumor cells together with CD3+ effector T cells without immunoreceptor and regulatory T cells developed earlier tumors with faster growth kinetics compared to mice that were inoculated with tumor cells, CD3+ T cells and CD4+CD25- control T cells. Using effector T cells that were equipped with a recombinant CEA-specific CD3-zeta immunoreceptor, 2 of 5 mice developed a tumor in the presence of regulatory T cells while none of the mice developed a tumor in the absence of regulatory T cells. Taken together, regulatory T cells obviously impair an antigen-specific, anti-tumor T cell attack in vivo. This seems to be due to repression of proliferation of the effector T cells and not to diminished cytotoxicity. These findings have major impact on the design of clinical studies involving adoptively transferred effector T cells.

scholarly journals Apoptotic tumor cells are superior to tumor cell lysate, and tumor cell RNA in induction of autologous T cell response in B-CLL

Leukemia ◽  
2004 ◽  
Vol 18 (11) ◽  
pp. 1810-1815 ◽  
Author(s):  
P Kokhaei ◽  
A Choudhury ◽  
R Mahdian ◽  
J Lundin ◽  
A Moshfegh ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Response ◽  
T Cell Response ◽  
Cell Lysate ◽  
Tumor Cell Lysate

scholarly journals CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy

2020 ◽  
Vol 8 (2) ◽  
pp. e000905 ◽  
Author(s):  
Hongfei Wang ◽  
Yixuan Sun ◽  
Xiuman Zhou ◽  
Chunxia Chen ◽  
Ling Jiao ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Cell Response ◽  
Regulatory Protein ◽  
T Cell Response ◽  
Antitumor Effects ◽  
Pathogen Invasion

BackgroundImmunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate immune cells, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, resisting tumor cells and promoting adaptive immune response. CD47 is found to be overexpressed on tumor cells and act as a don’t eat me’ signal, which contributes to immune evasion. Macrophages mediated phagocytosis via blockade CD47/SIRPα (signal regulatory protein alpha) interaction was proved to induce effective antitumor immune response.MethodsA novel peptide pep-20, specifically targeting CD47 and blocking CD47/SIRPα interaction, was identified via high-throughput phage display library bio-panning. The capability to enhance the macrophage-mediated phagocytosis activities and antitumor effects of pep-20 were investigated. The mechanism of pep-20 to induce T-cell response was explored by ex vivo analysis and confirmed via macrophage depleting strategy. The structure-activity relationship and D-amino acid substitution of pep-20 were also studied. The antitumor effects and mechanism of a proteolysis resistant D-amino acid derivate pep-20-D12 combined with irradiation (IR) were also investigated.ResultsPep-20 showed remarkable enhancement of macrophage-mediated phagocytosis to both solid and hematologic tumor cells in vitro, and inhibited tumor growth in immune-competent tumor-bearing mice. Furthermore, pep-20 promoted macrophages to mobilize the antitumor T-cell response with minimal toxicity. Furthermore, systemic administration of the derivate pep-20-D12 showed robust synergistic antitumor efficacy in combination with IR.ConclusionIn summary, these results demonstrated that CD47/SIRPα blocking peptides, pep-20 and its derivate, could serve as promising candidates to promote macrophages-mediated phagocytosis and immune response in cancer immunotherapy.

scholarly journals A Novel 62-Kilodalton Egg Antigen fromSchistosoma mansoni Induces a Potent CD4+ T Helper Cell Response in the C57BL/6 Mouse

1999 ◽  
Vol 67 (4) ◽  
pp. 1729-1735 ◽  
Author(s):  
Hiroko Asahi ◽  
Hector J. Hernandez ◽  
Miguel J. Stadecker
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
T Cell Response ◽  
T Helper ◽  
Th Cells ◽  
Cytokine Analysis ◽  
Egg Antigen

ABSTRACT In infection with Schistosoma mansoni, hepatic granuloma formation is mediated by CD4+ T helper (Th) cells sensitized to schistosomal egg antigens. There is considerable variation among infected individuals with respect to both severity of disease and the T-cell response to egg antigens. In the BL/6 mouse, the egg granulomas are relatively small and the relevant sensitizing egg antigens are largely unknown. We investigated the CD4+ Th cell response of infected BL/6 mice to egg antigens fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and found a prominent lymphoproliferative response to be directed against a 62-kDa component. With the aid of a specific T-cell hybridoma, 4E6, the 62-kDa antigen was isolated; following partial digestion with endoproteinase Glu-C, an internal amino acid sequence was found to be identical with one present in the enzyme phosphoenolpyruvate carboxykinase (PEPCK) of the organisms Caenorhabditis elegans and Treponema pallidum and to differ by one residue from PEPCK of various other species. In CD4+ Th cells from 7.5- 8.5-week-infected BL/6 mice, the purified 62-kDa molecule elicited a potent proliferative response which, based on cytokine analysis, was of a mixed Th-1 and Th-2 type. Our results reveal a novel egg antigen of particular prominence in the BL/6 mouse and suggest that the immune response in schistosomiasis is a product of sensitization to egg antigens that may vary considerably in immunogenicity from strain to strain.

CD4+ Peptide Epitopes from the WT1 Oncoprotein Stimulate CD4+ and CD8+ T Cells That Recognize and Kill Leukemia and Solid Tumor Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3706-3706
Author(s):  
Rena J. May ◽  
Javier Pinilla ◽  
Tatyana Korontsvit ◽  
Victoriya Zakhaleva ◽  
Ronghua H. Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Solid Tumor ◽  
Cell Response ◽  
Hla Class Ii ◽  
T Cell Response ◽  
Peptide Epitope ◽  
Peptide Epitopes

Abstract Wilms tumor protein 1 (WT1) is a transcription factor over-expressed in several types of leukemias and solid tumors, making it an ideal target for immunotherapy. A number of class I binding WT1 peptides have been identified and shown to stimulate CD8+ T cells. These peptides are being tested as potential cancer vaccine candidates in a variety of clinical trials. However, the induction and maintenance of a robust memory CD8+ cytotoxic T cell response requires CD4+ T cell help. Herein we report the identification of three HLA Class II peptide epitopes of WT1 using the SYFPEITHI and RANKPEP predictive algorithms. Peptides 328–349 and 423–441 are able to stimulate a peptide specific CD4+ response that can recognize WT1 positive tumor cells in multiple HLA-DRB*1 settings, as determined by IFN-gamma ELISPOT assays. Due to the highly polymorphic nature of the HLA class II alleles, such broad reactivity is critical in the development of a universal therapeutic. In addition, we identified a WT1 CD4+ peptide epitope (122–140) that lies within close proximity to a previously identified CD8+ peptide epitope (126–134). Residue 126 was mutated from an Arginine (R) to a Tyrosine (Y) thereby embedding a synthetic immunogenic analog CD8+ peptide that was previously designed to improve immunogenicity and induce a potent CD8+ response. Mutated peptide 122–140 is able to induce a CD4+ and cytotoxic CD8+ WT1 specific T cell response that can recognize the native WT1 epitopes on the surface of human CML and solid tumor cells. Cross-priming experiments demonstrated that APCs pulsed with either CML or mesothelioma tumor lysates can process and present each of the CD4+ peptides identified. These studies provide the rationale for using the three WT1 CD4+ peptides in conjunction with CD8+ peptide epitopes to vaccinate patients with WT1 expressing cancers.

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