scholarly journals Depletion of CD4+CD25high regulatory T cells from tumor infiltrating lymphocytes predominantly induces Th1 type immune response in vivo which inhibits tumor growth in adoptive immunotherapy

2009 ◽  
Vol 8 (1) ◽  
pp. 66-72 ◽  
Author(s):  
Lin Xu ◽  
Wei Xu ◽  
Zhenggang Jiang ◽  
Feng Zhang ◽  
Yiwei Chu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Growth ◽  
Adoptive Immunotherapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

In Vivo-Generated Antigen-Specific Regulatory T Cells Treat Autoimmunity Without Compromising Antibacterial Immune Response

2014 ◽  
Vol 6 (241) ◽  
pp. 241ra78-241ra78 ◽  
Author(s):  
S. Kasagi ◽  
P. Zhang ◽  
L. Che ◽  
B. Abbatiello ◽  
T. Maruyama ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells

Prolongation of survival following depletion of CD4+CD25+ regulatory T cells in mice with experimental brain tumors

2006 ◽  
Vol 105 (3) ◽  
pp. 430-437 ◽  
Author(s):  
Abdeljabar El Andaloussi ◽  
Yu Han ◽  
Maciej S. Lesniak
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Brain Tumors ◽  
Malignant Gliomas ◽  
Tumor Infiltrating Lymphocytes ◽  
Treg Cells ◽  
Separate Experiment ◽  
The Central Nervous System ◽  
Novel Target ◽  
Infiltrating Lymphocytes

Object Regulatory CD4+CD25+ T cells have been shown to play an important role in the regulation of the immune response. Whereas the presence of these cells has been associated with immune suppression, the lack of regulatory T (Treg) cells has been shown to induce autoimmunity. The purpose of this study was to define the role of Treg cells in tumors of the central nervous system (CNS). Methods The authors implanted syngeneic GL261 tumor cells in the brains or flanks of C57BL/6 mice. The resulting tumors were later removed at specific time points, and the presence of tumor-infiltrating lymphocytes was analyzed by performing flow cytometry for the presence of Treg cells. In a separate experiment, mice with GL261 tumors were treated with injections of anti-CD25 monoclonal antibody (mAb) to determine whether depletion of Treg cells may have an impact on the length of survival in mice with brain tumors. Tumor-infiltrating lymphocytes isolated from mice with GL261 tumors were found to have a significant increase in the presence of Treg cells compared with control lymphocytes (p < 0.05). Moreover, Treg cells isolated in murine brain tumors expressed FoxP3, CTLA-4, and CD62L. Mice treated with anti-CD25 mAb lived significantly longer than tumor-bearing control animals (p < 0.05). An analysis of brains in surviving animals showed a depletion of CD4+CD25+ T cells. Conclusions The results of this study indicate that CD4+CD25+ Treg cells play an important role in suppressing the immune response to CNS tumors. These Treg cells may therefore represent a potentially novel target for immunotherapy of malignant gliomas.

Clinical application of retroviral gene transfer in oncology: results of a French study with tumor-infiltrating lymphocytes transduced with the gene of resistance to neomycin.

1995 ◽  
Vol 13 (2) ◽  
pp. 410-418 ◽  
Author(s):  
Y Merrouche ◽  
S Negrier ◽  
C Bain ◽  
V Combaret ◽  
A Mercatello ◽  
...  
Keyword(s):  
Adoptive Immunotherapy ◽  
Human Lymphocytes ◽  
Marker Gene ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Pcr Analysis ◽  
Gene Marker ◽  
Gene Transduction ◽  
Infiltrating Lymphocytes

PURPOSE Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) has been reported to mediate tumor regression in some human cancers. To define better the biologic characteristics of TIL, especially survival and distribution in vivo, we performed a gene-marker study in patients with advanced malignancies. PATIENTS AND METHODS We treated five patients with metastatic melanoma or renal cell carcinoma with adoptive immunotherapy. TIL were genetically modified, before their infusion, using a recombinant retroviral vector that contained the marker gene coding for resistance to neomycin (NeoR). RESULTS All of the patients tolerated the treatment well and none of the theoretic safety hazards due to the retroviral gene transduction was observed. The presence of the NeoR gene in TIL was detected by Southern blot analysis, with an efficiency of transduction that ranged from 1% to 26%. With polymerase chain reaction (PCR) analysis, we demonstrated that gene-modified TIL can survive for several months after reinjection, since positive blood samples were observed up to day 260 following reinjection. Eight malignant biopsy specimens were obtained from three patients after cell infusion. TIL were detected in only four of these eight tumor deposits on days 7 and 260. CONCLUSION These results confirm the feasibility and safety of using in vitro retroviral gene transduction in human lymphocytes to analyze their in vivo distribution for further therapeutic applications. However, a selective and prolonged retention of TIL at the tumor site was not found in this study.

scholarly journals Activation of natural regulatory T cells by IgG Fc–derived peptide “Tregitopes”

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3303-3311 ◽  
Author(s):  
Anne S. De Groot ◽  
Leonard Moise ◽  
Julie A. McMurry ◽  
Erik Wambre ◽  
Laurence Van Overtvelt ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Regulatory T Cell ◽  
Mononuclear Cells ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear ◽  
Murine Homologue

Abstract We have identified at least 2 highly promiscuous major histocompatibility complex class II T-cell epitopes in the Fc fragment of IgG that are capable of specifically activating CD4+CD25HiFoxP3+ natural regulatory T cells (nTRegs). Coincubation of these regulatory T-cell epitopes or “Tregitopes” and antigens with peripheral blood mononuclear cells led to a suppression of effector cytokine secretion, reduced proliferation of effector T cells, and caused an increase in cell surface markers associated with TRegs such as FoxP3. In vivo administration of the murine homologue of the Fc region Tregitope resulted in suppression of immune response to a known immunogen. These data suggest that one mechanism for the immunosuppressive activity of IgG, such as with IVIG, may be related to the activity of regulatory T cells. In this model, regulatory T-cell epitopes in IgG activate a subset of nTRegs that tips the resulting immune response toward tolerance rather than immunogenicity.

scholarly journals Generating CAR T cells from tumor-infiltrating lymphocytes

2021 ◽  
Vol 9 ◽  
pp. 251513552110171
Author(s):  
Jane K. Mills ◽  
Melissa A. Henderson ◽  
Lauren Giuffrida ◽  
Pasquale Petrone ◽  
Jennifer A. Westwood ◽  
...  
Keyword(s):  
T Cells ◽  
Adoptive Cell Therapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Proliferative Potential ◽  
Melanoma Tumor ◽  
Cell Therapies ◽  
Nsg Mice ◽  
Car T ◽  
Infiltrating Lymphocytes

Background: Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising, though limited, efficacy against melanoma. Methods: We designed a model system to explore the efficacy of dual specific T cells derived from melanoma patient TILs by transduction with a Her2-specific CAR. Results: Metastatic melanoma cells in our biobank constitutively expressed Her2 antigen. CAR-TIL produced greater amounts of IFN compared with parental TIL, when co-cultured with Her2 expressing tumor lines, including autologous melanoma tumor lines, although no consistent increase in cytotoxicity by TIL was afforded by expression of a CAR. Results of an in vivo study in NSG mice demonstrated tumor shrinkage when CAR-TILs were used in an adoptive cell therapy protocol. Conclusion: Potential limitations of transduced TIL in our study included limited proliferative potential and a terminally differentiated phenotype, which would need addressing in further work before consideration of clinical translation.

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