scholarly journals Priming of tumor-specific T cells in the draining lymph nodes after immunization with interleukin 2-secreting tumor cells: three consecutive stages may be required for successful tumor vaccination.

1995 ◽  
Vol 92 (12) ◽  
pp. 5540-5544 ◽  
Author(s):  
G. Maass ◽  
W. Schmidt ◽  
M. Berger ◽  
F. Schilcher ◽  
F. Koszik ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Interleukin 2 ◽  
Tumor Vaccination ◽  
Draining Lymph Nodes

scholarly journals CD40 Ligand Promotes Priming of Fully Potent Antitumor CD4+ T Cells in Draining Lymph Nodes in the Presence of Apoptotic Tumor Cells

2001 ◽  
Vol 167 (10) ◽  
pp. 5678-5688 ◽  
Author(s):  
Nanae Fujita ◽  
Hiroshi Kagamu ◽  
Hirohisa Yoshizawa ◽  
Kazuhisa Itoh ◽  
Hideyuki Kuriyama ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Cd4 T Cells ◽  
Cd40 Ligand ◽  
Draining Lymph Nodes

scholarly journals Regulatory T cells with superior immunosuppressive capacity emigrate from the inflamed colon to draining lymph nodes

2017 ◽  
Vol 11 (2) ◽  
pp. 437-448 ◽  
Author(s):  
Y Nakanishi ◽  
R Ikebuchi ◽  
T Chtanova ◽  
Y Kusumoto ◽  
H Okuyama ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Draining Lymph Nodes

scholarly journals 793 Targeting engineered interleukin-2 (IL-2) to antigen specific T cells via novel biologic platforms

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A828-A828
Author(s):  
Raymond Moniz ◽  
Ahmet Vakkasoglu ◽  
Zohra Merazga ◽  
Tina Daigneault ◽  
Steve Quayle ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Interleukin 2 ◽  
Binding Pocket ◽  
Tumor Escape ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Cell Repertoire

BackgroundA key challenge with IL-2 immunotherapy for cancers is lack of selectivity for anti-tumor immune cells and safety liabilities related to indiscriminate activation of immune cells. The CUE-100 series of Immuno-STATs (ISTs) are designed to selectively activate tumor-specific T cells while avoiding IL-2 toxicities due to systemic activation. CUE-100 series ISTs are rationally engineered Fc fusion proteins comprised of bivalent tumor-peptide-HLA (pHLA) complexes and four affinity-attenuated IL-2 molecules to preferentially engage and activate tumor-specific T cells directly in the patient. Emerging clinical data from our lead candidate CUE-101, which targets HPV-specific T cells in 2L+ R/M HNSCCC, provides PoC for the approach and builds confidence for broad applications in numerous cancers. Building on the CUE-100 series framework, our Neo-STAT (NST) platform contains HLA molecules manufactured with an “empty” peptide-binding pocket, into which diverse tumor-peptides can be chemically conjugated, hence addressing tumor heterogeneity in a cost- and time-efficient manner. Our RDI-STAT (Re-Directed Immuno-STAT) platform further expands the CUE-100 series by redirecting the pre-existing protective viral-specific T cell repertoire to target tumor cells via scFv moieties. RDI-STATs are designed to circumvent potential tumor escape mechanisms linked to HLA loss or defects in antigen-presenting pathways. We present here preclinical data supporting the mechanism of action of these platforms to enhance anti-tumor immune responses.MethodsNSTs were engineered with “empty” HLA-A*0201, into which relevant antigenic peptides were conjugated, and assessed for capacity to expand T cells. RDI-STATs were engineered with TAA-specific scFv and viral-specific pHLA complexes, and assessed for their capacity to induce redirected killing of tumor cells while avoiding systemic activation of all T cells.ResultsThe NST platform demonstrated that different T cell epitopes can be efficiently conjugated into the HLA-binding pocket, and that these molecules activate and expand antigen specific T cells in vitro. RDI-STATs were able to expand anti-viral T cell repertoires and drive anti-viral T cell redirected killing of TAA-expressing cells. In contrast to pan anti-CD3 bispecific molecules, RDI-STATs demonstrated significantly lower induction of pro-inflammatory cytokines.ConclusionsThe IST, NST, and RDI-STAT platforms provide novel opportunities for selective targeting of IL-2 to tumor-relevant T cells while avoiding global immune activation and cytokine release. The scalability and versatility of NSTs highlight the potential to target multiple TAA T cell responses, while RDI-STATs highlight a novel means to harness antiviral immunity against cancer, especially in cases where the tumor may escape immune detection due to loss of HLA.

scholarly journals Regulatory T Cells Sequentially Migrate from Inflamed Tissues to Draining Lymph Nodes to Suppress the Alloimmune Response

Immunity ◽  
2009 ◽  
Vol 30 (3) ◽  
pp. 458-469 ◽  
Author(s):  
Nan Zhang ◽  
Bernd Schröppel ◽  
Girdhari Lal ◽  
Claudia Jakubzick ◽  
Xia Mao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Draining Lymph Nodes

scholarly journals Activation-induced cell death of self-reactive regulatory T cells drives autoimmunity

2019 ◽  
Vol 116 (52) ◽  
pp. 26788-26797
Author(s):  
Ester Badami ◽  
Olivier N. F. Cexus ◽  
Sonia Quaratino
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Lymph Nodes ◽  
Autoimmune Thyroiditis ◽  
The Self ◽  
Thyroid Peroxidase ◽  
Activation Induced Cell Death ◽  
Self Antigen ◽  
Draining Lymph Nodes

Activation of self-reactive T cells is a major driver to autoimmunity and is suppressed by mechanisms of regulation. In a humanized model of autoimmune thyroiditis, we investigated the mechanism underlying break of tolerance. Here, we found that a human TCR specific for the self-antigen thyroid peroxidase (TPO) is positively selected in the thymus of RAG KO mice on both T effector (Teff) and T regulatory (Treg) CD4+Foxp3+cells. In vivo Teffare present in all immune organs, whereas the TPO-specific Tregare present in all lymphoid organs with the exception of the thyroid-draining lymph nodes. We suggest that the presence of TPO in the thyroid draining lymph nodes induces the activation of Teffand the depletion of Tregvia activation-induced cell death (AICD). Our findings provide insights on the failure of the mechanisms of immune tolerance, with potential implications in designing immunotherapeutic strategies.

Phase II Trial of Autologous Tumor Vaccination, Anti-CD3-Activated Vaccine-Primed Lymphocytes, and Interleukin-2 in Stage IV Renal Cell Cancer

2003 ◽  
Vol 21 (5) ◽  
pp. 884-890 ◽  
Author(s):  
Alfred E. Chang ◽  
Qiao Li ◽  
Guihua Jiang ◽  
Donna M. Sayre ◽  
Thomas M. Braun ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Stage Iv ◽  
Autologous Tumor ◽  
Cytokine Release

Purpose: Previous preclinical and clinical studies have demonstrated that autologous tumor vaccines can induce relatively specific tumor-reactive T cells in draining lymph nodes. The adoptive transfer of these cells can result in tumor regression. Patients and Methods: Patients with stage IV renal cell cancer (RCC) were vaccinated with irradiated autologous tumor cells admixed with Calmette-Guérin bacillus. Approximately 7 days later, vaccine-primed lymph nodes (VPLNs) were harvested and the lymphoid cells secondarily activated with anti-CD3 monoclonal antibody and expanded in interleukin 2 (IL-2). The activated cells were subsequently infused intravenously along with the concomitant administration of bolus IL-2 (360,000 U/kg intravenously × 15 doses). Results: Thirty-nine patients were entered onto the study, of whom 34 completed an initial course of cell therapy consisting of a mean (SEM) number of 4.3 (2.2) × 1010 VPLN cells. Among subjects who received cell therapy, there were nine responses (four complete responses [CRs] and five partial responses [PRs]), for an overall response rate of 27%. The durations of the CRs were > 48, 45, > 35, and 12 months, and the durations of the PRs were > 63, 48, 15, 12, and 4 months. Cultured tumor cells were available to assess in vitro cytokine release of VPLN cells in 24 subjects. The median cytokine release ratio of interferon gamma (IFNγ) to IL-10 for responders and nonresponders was 992 and 5, respectively, which was significantly different (P = .047). Conclusion: The treatment protocol resulted in durable tumor responses in patients with advanced RCC. The ratio of IFNγ and IL-10 cytokines released in response to tumor by the VPLN cells was a significant correlate with tumor response.

Sign in / Sign up

Export Citation Format

Share Document