scholarly journals S-540956, a CpG Oligonucleotide Annealed to a Complementary Strand With an Amphiphilic Chain Unit, Acts as a Potent Cancer Vaccine Adjuvant by Targeting Draining Lymph Nodes

2021 ◽  
Vol 12 ◽  
Author(s):  
Takayuki Nakagawa ◽  
Tetsuya Tanino ◽  
Motoyasu Onishi ◽  
Soichi Tofukuji ◽  
Takayuki Kanazawa ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Specific Antigen ◽  
Peptide Vaccine ◽  
Vaccine Antigen ◽  
Complementary Strand ◽  
Peptide Vaccines ◽  
Complementary Sequence ◽  
Hpv E7 ◽  
Draining Lymph Nodes

Robust induction of cancer-antigen-specific CD8+ T cells is essential for the success of cancer peptide vaccines, which are composed of a peptide derived from a cancer-specific antigen and an immune-potentiating adjuvant, such as a Toll-like receptor (TLR) agonist. Efficient delivery of a vaccine antigen and an adjuvant to antigen-presenting cells in the draining lymph nodes (LNs) holds key to maximize vaccine efficacy. Here, we developed S-540956, a novel TLR9-agonistic adjuvant consisting of B-type CpG ODN2006 (also known as CpG7909), annealed to its complementary sequence oligodeoxynucleotide (ODN) conjugated to a lipid; it could target both a cancer peptide antigen and a CpG-adjuvant in the draining LNs. S-540956 accumulation in the draining LNs and activation of plasmacytoid dendritic cells (pDCs) were significantly higher than that of ODN2006. Mechanistic analysis revealed that S-540956 enhanced the induction of MHC class I peptide-specific CD8+ T cell responses via TLR9 in a CD4+ T cell-independent manner. In mice, the therapeutic effect of S-540956-adjuvanted with a human papillomavirus (HPV)-E7 peptide vaccine against HPV-E7-expressing TC-1 tumors was significantly better than that of an ODN2006-adjuvanted vaccine. Our findings demonstrate a novel adjuvant discovery with the complementary strand conjugated to a lipid, which enabled draining LN targeting and increased ODN2006 accumulation in draining LNs, thereby enhancing the adjuvant effect. Our findings imply that S-540956 is a promising adjuvant for cancer peptide vaccines and has a high potential for applications in various vaccines, including recombinant protein vaccines.

scholarly journals HETEROGENEITY OF ANTIBODY-FORMING CELLS

1969 ◽  
Vol 129 (5) ◽  
pp. 1029-1044 ◽  
Author(s):  
Cesare Bosman ◽  
Joseph D. Feldman ◽  
Edgar Pick
Keyword(s):  
Lymph Nodes ◽  
Plasma Cells ◽  
Specific Antigen ◽  
Cell Suspensions ◽  
Electron Microscopic ◽  
Cytoplasmic Vacuoles ◽  
Draining Lymph Nodes

Cell suspensions from draining lymph nodes of immune and nonimmune rats were reacted in vitro with 125I-labeled antigens. In light microscopic radioautographs of smears, 17% of the immunized cells were tagged by specific antigen; 2.0% of control cells were positive. In electron microscopic radioautographs, 90% of the labeled elements from immune donors were lymphocytes, blast and plasma cells; 10% were monocytes-macrophages or other elements, including naked nuclei. 15% of the labeled cells from control materials were lymphocytes and plasma cells, while 85% were monocytes-macrophages and naked nuclei. Within cell suspensions derived from immunized animals there were almost twice as many lymphocytes marked by isotope as plasma cells, and the lymphocytes ranged in morphology from mature monoribosomal elements to immature polyribosomal cells. Antibody-forming cells fixed labeled antigen at their surfaces. The monocyte-macrophage class was distinguished by a high mean grain count and by distribution of grains within cytoplasmic vacuoles and lysosomes.

scholarly journals In vivo two-photon imaging of T cell motility in joint-draining lymph nodes in a mouse model of rheumatoid arthritis

2012 ◽  
Vol 278 (1-2) ◽  
pp. 158-165 ◽  
Author(s):  
Tamás Kobezda ◽  
Sheida Ghassemi-Nejad ◽  
Tibor T. Glant ◽  
Katalin Mikecz
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Mouse Model ◽  
Lymph Nodes ◽  
Cell Motility ◽  
Two Photon ◽  
Photon Imaging ◽  
Two Photon Imaging ◽  
Draining Lymph Nodes

scholarly journals Identification of Melanoma-reactive CD4+ T-Cell Subsets From Human Melanoma Draining Lymph Nodes

2016 ◽  
Vol 39 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Mei Zhang ◽  
Hallie Graor ◽  
Lu Yan ◽  
Julian Kim
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Human Melanoma ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Draining Lymph Nodes

scholarly journals Dermal Vγ4 + γδ T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8 + T-Cell Activity through TNF-α Production

2015 ◽  
Vol 135 (4) ◽  
pp. 1007-1015 ◽  
Author(s):  
Satoshi Nakamizo ◽  
Gyohei Egawa ◽  
Michio Tomura ◽  
Shunsuke Sakai ◽  
Soken Tsuchiya ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Cell Activity ◽  
Γδ T Cells ◽  
Cd8 T Cell ◽  
Tnf Α ◽  
Draining Lymph Nodes

scholarly journals Analysis of T-Cell Receptor Vβ Gene Repertoires after Immune Stimulation and in Malignancy by Use of Padlock Probes and Microarrays

2005 ◽  
Vol 51 (4) ◽  
pp. 768-775 ◽  
Author(s):  
Johan Banér ◽  
Per Marits ◽  
Mats Nilsson ◽  
Ola Winqvist ◽  
Ulf Landegren
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Peripheral Blood ◽  
Tumor Infiltrating Lymphocytes ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Padlock Probes ◽  
Enterotoxin B ◽  
Infiltrating Lymphocytes ◽  
Draining Lymph Nodes

Abstract Background: Detection of expanded T-cell clones, identified by their receptor (TCR) repertoires, can assist diagnosis and guide therapy in infectious, inflammatory, and autoimmune conditions as well as in tumor immunotherapy. Analysis of tumor-infiltrating lymphocytes often reveals preferential use of one or a few TCR Vβ genes, compared with peripheral blood, indicative of a clonal response against tumor antigens. Methods: To simultaneously measure the relative expression of all Vβ gene families, we combined highly specific and sensitive oligonucleotide reagents, called padlock probes, with a microarray read-out format. T-Cell cDNA was combined with a pool of Vβ subfamily-specific padlock probes. Reacted probes were selectively amplified and the products hybridized to a microarray, from which the Vβ subfamily distribution in each sample could be determined relative to a control sample. Results: In lymphocytes stimulated with the superantigen staphylococcal enterotoxin B, we detected expansions at the mRNA level of TCR subfamilies previously shown to respond to staphylococcal enterotoxin B. Expansions of the same Vβ families could also be detected by flow cytometry. In samples from two bladder cancer patients, we detected predominant representations of specific Vβ subfamilies in both tumor-infiltrating lymphocytes and in the draining lymph nodes, but not in non-tumor-draining lymph nodes or peripheral blood. Several expression profiles from draining lymph nodes in patients with malignant melanoma were divergent from profiles seen in non-tumor-draining lymph nodes. Conclusion: Padlock probe-based parallel analysis of TCR Vβ gene distributions provides an efficient method for screening multiple samples for T-cell clonal expansions with reduced labor and time of analysis compared with traditional methods.

scholarly journals Infection-Induced Dermal Lymphatic Zippering Restricts Viral Dissemination from Skin and Promotes Anti-Viral CD8+ T Cell Expansion

2021 ◽  
Author(s):  
Madeline J. Churchill ◽  
Haley du Bois ◽  
Taylor A. Heim ◽  
Tenny Mudianto ◽  
Maria M. Steele ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Vaccinia Virus ◽  
Host Defense ◽  
Lymphatic Vessels ◽  
T Cell Responses ◽  
Lymphatic Capillary ◽  
Viral Dissemination ◽  
Cell Responses ◽  
Draining Lymph Nodes

AbstractLymphatic vessels are often considered passive conduits that rapidly flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that dermal lymphatic transport is dynamic and contributes to innate host defense during viral infection. We demonstrate that cutaneous vaccinia virus infection activates the tightening of lymphatic interendothelial junctions, termed zippering, in a VEGFA/VEGFR2-dependent manner. Both antibody-mediated blockade of VEGFA/VEGFR2 and lymphatic-specific deletion of Vegfr2 impaired lymphatic capillary zippering and increased fluid flux out of tissue. Strikingly, inhibition of lymphatic zippering allows viral dissemination to draining lymph nodes independent of dendritic cell migration and impairs CD8+ T cell priming. These data indicate that infection-induced dermal lymphatic capillary zippering is a context-dependent, active mechanism of innate host defense that limits interstitial fluid and virion flux and promotes protective, anti-viral CD8+ T cell responses.SummaryCutaneous infection with vaccinia virus induces VEGFR2-dependent dermal lymphatic capillary zippering. This tightening of lymphatic junctions exacerbates tissue edema, sequesters virus, and promotes anti-viral CD8+ T cell responses. Dermal lymphatic capillaries are therefore an active component of innate host defense.

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