scholarly journals Protective Immunosurveillance and Therapeutic Antitumor Activity of γδ T Cells Demonstrated in a Mouse Model of Prostate Cancer

2008 ◽  
Vol 180 (9) ◽  
pp. 6044-6053 ◽  
Author(s):  
Zhiyong Liu ◽  
Isam-Eldin A. Eltoum ◽  
Ben Guo ◽  
Benjamin H. Beck ◽  
Gretchen A. Cloud ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Antitumor Activity ◽  
Mouse Model ◽  
Γδ T Cells

An obligate role for T-cell receptor αβ+ T cells but not T-cell receptor γδ+ T cells, B cells, or CD40/CD40L interactions in a mouse model of atopic dermatitis

2001 ◽  
Vol 107 (2) ◽  
pp. 359-366 ◽  
Author(s):  
Amy L. Woodward ◽  
Jonathan M. Spergel ◽  
Harri Alenius ◽  
Emiko Mizoguchi ◽  
Atul K. Bhan ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
B Cells ◽  
Mouse Model ◽  
T Cell Receptor ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
Αβ T Cells

γδ T cells for immune therapy of patients with lymphoid malignancies

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 200-206 ◽  
Author(s):  
Martin Wilhelm ◽  
Volker Kunzmann ◽  
Susanne Eckstein ◽  
Peter Reimer ◽  
Florian Weissinger ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antitumor Activity ◽  
Low Dose ◽  
Γδ T Cells ◽  
Low Grade ◽  
Treatment Schedule ◽  
Γδ T Cell

Abstract There is increasing evidence that γδ T cells have potent innate antitumor activity. We described previously that synthetic aminobisphosphonates are potent γδ T cell stimulatory compounds that induce cytokine secretion (ie, interferon γ [IFN-γ]) and cell-mediated cytotoxicity against lymphoma and myeloma cell lines in vitro. To evaluate the antitumor activity of γδ T cells in vivo, we initiated a pilot study of low-dose interleukin 2 (IL-2) in combination with pamidronate in 19 patients with relapsed/refractory low-grade non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). The objectives of this trial were to determine toxicity, the most effective dose for in vivo activation/proliferation of γδ T cells, and antilymphoma efficacy of the combination of pamidronate and IL-2. The first 10 patients (cohort A) who entered the study received 90 mg pamidronate intravenously on day 1 followed by increasing dose levels of continuous 24-hour intravenous (IV) infusions of IL-2 (0.25 to 3 × 106 IU/m2) from day 3 to day 8. Even at the highest IL-2 dose level in vivo, γδ T-cell activation/proliferation and response to treatment were disappointing with only 1 patient achieving stable disease. Therefore, the next 9 patients were selected by positive in vitro proliferation of γδ T cells in response to pamidronate/IL-2 and received a modified treatment schedule (6-hour bolus IV IL-2 infusions from day 1-6). In this patient group (cohort B), significant in vivo activation/proliferation of γδ T cells was observed in 5 patients (55%), and objective responses (PR) were achieved in 3 patients (33%). Only patients with significant in vivo proliferation of γδ T cells responded to treatment, indicating that γδ T cells might contribute to this antilymphoma effect. Overall, administration of pamidronate and low-dose IL-2 was well tolerated. In conclusion, this clinical trial demonstrates, for the first time, that γδ T-cell–mediated immunotherapy is feasible and can induce objective tumor responses. (Blood. 2003;102:200-206)

Zoledronate Stimulates γδ T Cells in Prostate Cancer Patients

2009 ◽  
Vol 18 (10) ◽  
pp. 493-501 ◽  
Author(s):  
Michio Naoe ◽  
Yoshio Ogawa ◽  
Kumiko Takeshita ◽  
Jun Morita ◽  
Takeshi Shichijo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Γδ T Cells

scholarly journals Adoptively transferred ex vivo expanded γδ-T cells mediate in vivo antitumor activity in preclinical mouse models of breast cancer

2009 ◽  
Vol 122 (1) ◽  
pp. 135-144 ◽  
Author(s):  
Benjamin H. Beck ◽  
Hyung-Gyoon Kim ◽  
Hyunki Kim ◽  
Sharon Samuel ◽  
Zhiyong Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Antitumor Activity ◽  
Mouse Models ◽  
Ex Vivo ◽  
Γδ T Cells ◽  
In Vivo Antitumor Activity

scholarly journals Targeting Human γδ T Cells with Zoledronate and Interleukin-2 for Immunotherapy of Hormone-Refractory Prostate Cancer

2007 ◽  
Vol 67 (15) ◽  
pp. 7450-7457 ◽  
Author(s):  
Francesco Dieli ◽  
David Vermijlen ◽  
Fabio Fulfaro ◽  
Nadia Caccamo ◽  
Serena Meraviglia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Interleukin 2 ◽  
Γδ T Cells ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

scholarly journals Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheumatoid Arthritis: A Morphological and Histological Evaluation

2022 ◽  
Vol 12 ◽  
Author(s):  
Kohei Nagai ◽  
Takenobu Ishii ◽  
Tatsukuni Ohno ◽  
Yasushi Nishii
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Mouse Model ◽  
Mandibular Condyle ◽  
Γδ T Cells ◽  
Histological Evaluation ◽  
Micro Ct ◽  
Layer Width ◽  
Temporomandibular Joints ◽  
Histological Staining

Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9−12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.

Vγ9Vδ2 T cells and zoledronate mediate antitumor activity in an orthotopic mouse model of human chondrosarcoma

Tumor Biology ◽  
2015 ◽  
Vol 37 (6) ◽  
pp. 7333-7344 ◽  
Author(s):  
L. Sun ◽  
Y. Li ◽  
Z. Jiang ◽  
J. Zhang ◽  
H. Li ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Activity ◽  
Mouse Model ◽  
Orthotopic Mouse Model ◽  
Human Chondrosarcoma ◽  
Vγ9vδ2 T Cells

Phase I study of AMG 160, a half-life extended bispecific T-cell engager (HLE BiTE immune therapy) targeting prostate-specific membrane antigen, in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5590-TPS5590 ◽  
Author(s):  
Ben Tran ◽  
Lisa Horvath ◽  
Matthew Rettig ◽  
Karim Fizazi ◽  
Martijn P. Lolkema ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Antitumor Activity ◽  
Phase I Study ◽  
Immune Therapy ◽  
Prostate Specific Membrane Antigen ◽  
Pet Ct ◽  
Specific Membrane

TPS5590 Background: Prostate-specific membrane antigen (PSMA) is a clinically validated therapeutic target for the imaging and treatment of mCRPC. AMG 160 is an HLE BiTE immune therapy designed to redirect T cells to cancer cells by binding to PSMA on cancer cells and CD3 on T cells. BiTE immune therapy leads to direct tumor cell killing, T-cell activation and expansion, and the creation of a pro-inflammatory tumor microenvironment. Combining AMG 160 with a PD-1 inhibitor may enhance antitumor activity by enabling sustained T-cell-dependent killing of tumor cells in the inflamed tumor microenvironment. Methods: NCT03792841 is a phase I study of AMG 160 as monotherapy (part 1) and in combination with pembrolizumab (part 2) in men with histologically/cytologically confirmed mCRPC who are refractory to a novel hormonal therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed 1–2 taxane regimens (or are medically unsuitable or have refused taxanes), who have ongoing castration with total serum testosterone ≤ 50 ng/dL, and have evidence of progressive disease. Patients who received prior PSMA radionuclide therapy may be eligible. Patients with CNS metastases, leptomeningeal disease, spinal cord compression, or active autoimmune disease will be excluded. Primary objectives are to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of AMG 160 given as monotherapy or in combination with pembrolizumab. Secondary objectives are to characterize pharmacokinetics and preliminary antitumor activity. Exploratory objectives include evaluation of potential pharmacodynamic and patient selection biomarkers, immunogenicity, and patient-reported pain and functional outcomes. The part 1 dose exploration will determine the MTD/RP2D of AMG 160. The part 1 dose expansion will confirm the safety and tolerability of the MTD/RP2D. The part 2 dose exploration will estimate the MTD/RP2D of AMG 160 in combination with pembrolizumab. Evaluation of preliminary antitumor activity will be based on RECIST 1.1 with Prostate Cancer Working Group 3 modifications, PSA response, CTC response, progression-free survival (radiographic and PSA), and overall survival. PSMA PET/CT and FDG PET/CT imaging will be used for evaluation of exploratory objectives. The study opened in February 2019 and is currently recruiting patients into both part 1 and part 2. Clinical trial information: NCT03792841 .

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