In vivo imaging of rat lymphocytes with an indium 111-labelled anti-T cell monoclonal antibody: a comparison with indium 111-labelled lymphocytes

1990 ◽  
Vol 16 (2) ◽  
pp. 69-76 ◽  
Author(s):  
Issa Loutfi ◽  
Patricia M. Chisholm ◽  
Debbie Bevan ◽  
John P. Lavender
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
In Vivo Imaging ◽  
Rat Lymphocytes ◽  
Indium 111

scholarly journals In vivo imaging of T cell delivery to tumors after adoptive transfer therapy

2007 ◽  
Vol 104 (30) ◽  
pp. 12457-12461 ◽  
Author(s):  
M. J. Pittet ◽  
J. Grimm ◽  
C. R. Berger ◽  
T. Tamura ◽  
G. Wojtkiewicz ◽  
...  
Keyword(s):  
T Cell ◽  
Adoptive Transfer ◽  
In Vivo Imaging ◽  
Cell Delivery ◽  
Adoptive Transfer Therapy

scholarly journals Total body CD4+ T cell dynamics in treated and untreated SIV infection revealed by in vivo imaging

JCI Insight ◽  
2018 ◽  
Vol 3 (13) ◽  
Author(s):  
Michele Di Mascio ◽  
Sharat Srinivasula ◽  
Insook Kim ◽  
Gorka Duralde ◽  
Alexis St. Claire ◽  
...  
Keyword(s):  
T Cell ◽  
In Vivo Imaging ◽  
Cd4 T Cell ◽  
Cell Dynamics ◽  
Siv Infection ◽  
Total Body

scholarly journals A Novel Approach for the Treatment of T Cell Malignancies: Targeting T Cell Receptor Vβ Families

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 631
Author(s):  
Jie Wang ◽  
Katarzyna Urbanska ◽  
Prannda Sharma ◽  
Reza Nejati ◽  
Lauren Shaw ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Lymphomas ◽  
Novel Approach ◽  
T Cell Malignancies

Peripheral T cell lymphomas (PTCLs) are generally chemotherapy resistant and have a poor prognosis. The lack of targeted immunotherapeutic approaches for T cell malignancies results in part from potential risks associated with targeting broadly expressed T cell markers, namely T cell depletion and clinically significant immune compromise. The knowledge that the T cell receptor (TCR) β chain in human α/β TCRs are grouped into Vβ families that can each be targeted by a monoclonal antibody can therefore be exploited for therapeutic purposes. Here, we develop a flexible approach for targeting TCR Vβ families by engineering T cells to express a chimeric CD64 protein that acts as a high affinity immune receptor (IR). We found that CD64 IR-modified T cells can be redirected with precision to T cell targets expressing selected Vβ families by combining CD64 IR-modified T cells with a monoclonal antibody directed toward a specific TCR Vβ family in vitro and in vivo. These findings provide proof of concept that TCR Vβ-family-specific T cell lysis can be achieved using this novel combination cell–antibody platform and illuminates a path toward high precision targeting of T cell malignancies without substantial immune compromise.

The Use of Monoclonal Antibody Directed Chimeric Antigen Receptors to Facilitate Conventional T Cell and Treg Control of GvHD and Tissue Tolerance in Murine Models

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3355-3355
Author(s):  
Antonio Pierini ◽  
Bettina Iliopoulou ◽  
Heshan Peiris ◽  
Magdiel Perez Cruz ◽  
Jeanette Baker ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Organ Transplantation ◽  
Adoptive Transfer ◽  
Skin Grafts ◽  
Mhc I ◽  
Cell Homing ◽  
University Patents

Abstract INTRODUCTION Regulatory T cells (Treg) modulate allograft immune responses and Treg-based cellular therapies can be used for prevention of graft-versus-host disease (GvHD) following hematopoietic cell transplantation and for prevention of allograft rejection following tissue or organ transplantation. Treg adoptive transfer has limitations including that Treg do not necessarily home to sites where they are needed and can become inactivated in inflammatory milieus. METHODS We used new technologies of T cell engineering to force the expression of a chimeric antigen receptor on T cells and Treg that recognizes labeled therapeutic monoclonal antibodies (mabCAR), allowing for precise control of their localization in vivo. The mabCAR recognizes fluorescein isothiocyanate (FITC) through a FITC-specific single-chain variable fragment fused to a CD28 and TCRζ costimulatory domain. Any monoclonal antibody (mab) coupled to FITC within its Fc domain can be recognized. We tested this approach with T cells and Treg to ameliorate GvHD and induce tolerance to pancreatic islet grafts. RESULTS We first tested our mabCAR construct in conventional T cells (Tcon) which when transfected and stimulated with a FITC-mab become activated and expressed higher levels of CD44 (p=0.0003), CD25 (p=0.009) and produced more IFNγ (p=0.04). To test if mabCAR transient transfection alters Tcon homing after adoptive transfer, we injected luc+ mabCAR Tcon directed against MAdCAM1 (a gut and lymph node endothelial integrin) or SDF1 (a chemokine mainly expressed in the bone marrow) into allogeneic hosts. MAdCAM1-directed Tcon mainly homed to the gut and lymph nodes, while SDF1-directed Tcon homed to bones and spleen. SDF1-directed Tcon induced a milder GvHD (p<0.001), demonstrating that cell homing impacts GvHD severity. We then tested mabCAR Treg ability to maintain their suppressive activity in vitro and in vivo. We found that mabCAR transiently transfected into Treg have increased ability to proliferate in response to anti-CD3/CD28 stimulatory beads (p<0.01) and highly suppress Tcon proliferation when co-cultured with allogeneic irradiated splenocytes. We injected MAdCAM1 directed Treg in an allogeneic GvHD model and these mabCAR Treg prolonged survival (p=0.03), improved GvHD score (p<0.001) and mouse weight profile (p<0.001), thus demonstrating that mabCAR Treg retain regulatory functions. Finally, we tested if mabCAR Treg could induce tolerance to allogeneic pancreatic islet grafts in sublethally irradiated hosts. Luc+gfp+ mabCAR Treg homed and expanded over time (p<0.05) to the site of the allogeneic islet grafts (right kidney capsule) when FITC-anti-allogeneic MHC-I mab directed the Treg as compared to isotype mab controls (see figure). Allo-MHC-I directed mabCAR-Treg prolonged allogeneic islet graft survival in comparison to isotype-mabCAR Treg (p=0.002) allowing for production of higher insulin levels. To assess if allo-MHC-I Treg promoted antigen-specific tolerance, we performed secondary skin graft transplantation. We found that mice which received MHC-I Treg showed a significant delay in the rejection of skin grafts from mice with the same MHC mismatch as the previous islet-allografts in comparison to third-party skin grafts (p=0.02) offering strong evidence that CAR-Treg could be used to enhance antigen-specific graft protection. CONCLUSION MabCAR expression can be used to control immune cell homing after transfer in different models according to localizing mab availability. We believe that the mabCAR approach may represent a new tool for optimizing cellular therapies to modulate GvHD and for inducing tolerance in islet and organ transplantation. Figure Figure. Disclosures Pierini: Stanford University: Patents & Royalties. Iliopoulou:Stanford University: Patents & Royalties. Negrin:Stanford University: Patents & Royalties. Kim:Stanford University: Patents & Royalties. Meyer:Stanford University: Patents & Royalties.

scholarly journals Identification of the Neoplastically Transformed Cells in Marek's Disease Herpesvirus-Induced Lymphomas: Recognition by the Monoclonal Antibody AV37

2002 ◽  
Vol 76 (14) ◽  
pp. 7276-7292 ◽  
Author(s):  
Shane C. Burgess ◽  
T. Fred Davison
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Lymphoma Cell ◽  
Marek's Disease ◽  
Transformed Cells ◽  
Marek’S Disease ◽  
Lymphoma Cells ◽  
Transformed Cell Lines ◽  
First Time

ABSTRACT Understanding the interactions between herpesviruses and their host cells and also the interactions between neoplastically transformed cells and the host immune system is fundamental to understanding the mechanisms of herpesvirus oncology. However, this has been difficult as no animal models of herpesvirus-induced oncogenesis in the natural host exist in which neoplastically transformed cells are also definitively identified and may be studied in vivo. Marek's disease (MD) herpesvirus (MDV) of poultry, although a recognized natural oncogenic virus causing T-cell lymphomas, is no exception. In this work, we identify for the first time the neoplastically transformed cells in MD as the CD4+ major histocompatibility complex (MHC) class Ihi, MHC class IIhi, interleukin-2 receptor α-chain-positive, CD28lo/−, phosphoprotein 38-negative (pp38−), glycoprotein B-negative (gB−), αβ T-cell-receptor-positive (TCR+) cells which uniquely overexpress a novel host-encoded extracellular antigen that is also expressed by MDV-transformed cell lines and recognized by the monoclonal antibody (MAb) AV37. Normal uninfected leukocytes and MD lymphoma cells were isolated directly ex vivo and examined by flow cytometry with MAb recognizing AV37, known leukocyte antigens, and MDV antigens pp38 and gB. CD28 mRNA was examined by PCR. Cell cycle distribution and in vitro survival were compared for each lymphoma cell population. We demonstrate for the first time that the antigen recognized by AV37 is expressed at very low levels by small minorities of uninfected leukocytes, whereas particular MD lymphoma cells uniquely express extremely high levels of the AV37 antigen; the AV37hi MD lymphoma cells fulfill the accepted criteria for neoplastic transformation in vivo (protection from cell death despite hyperproliferation, presence in all MD lymphomas, and not supportive of MDV production); the lymphoma environment is essential for AV37+ MD lymphoma cell survival; pp38 is an antigen expressed during MDV-productive infection and is not expressed by neoplastically transformed cells in vivo; AV37+ MD lymphoma cells have the putative immune evasion mechanism of CD28 down-regulation; AV37hi peripheral blood leukocytes appear early after MDV infection in both MD-resistant and -susceptible chickens; and analysis of TCR variable β chain gene family expression suggests that MD lymphomas have polyclonal origins. Identification of the neoplastically transformed cells in MD facilitates a detailed understanding of MD pathogenesis and also improves the utility of MD as a general model for herpesvirus oncology.

scholarly journals In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages

2013 ◽  
Vol 110 (22) ◽  
pp. 9090-9095 ◽  
Author(s):  
I. A. Cockburn ◽  
R. Amino ◽  
R. K. Kelemen ◽  
S. C. Kuo ◽  
S.-W. Tse ◽  
...  
Keyword(s):  
T Cell ◽  
In Vivo Imaging ◽  
Cd8 T Cell

550 An Axl-targeting monoclonal antibody that inhibits Axl activity and potently stimulates the innate immune response

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A587-A587
Author(s):  
Diego Alvarado ◽  
Laura Vitale ◽  
Mike Murphy ◽  
Thomas O’Neill ◽  
Edward Natoli ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Cancer ◽  
Cell Activity ◽  
Negative Regulator

BackgroundAxl is a member of the TAM (Tyro3/Axl/MerTK) family of receptor tyrosine kinases and a negative regulator of innate immunity. Activation of Axl through its ligand Gas6 leads to suppression of myeloid cell activity, while its activation in tumor cells drives tumor growth, metastasis, and is associated with acquired resistance to targeted therapies, radiotherapy and chemotherapy.MethodsPurified monoclonal antibodies and variants thereof were tested in human cancer lines and primary human myeloid cells for effects on Axl signaling and immune activation, respectively.ResultsWe describe a humanized IgG1 Axl-targeting monoclonal antibody (mAb), CDX-0168, that binds to the ligand-binding domain of Axl with sub-nanomolar affinity and potently inhibits Gas6 binding. In tumor cells, CDX-0168 inhibits Gas6-dependent Axl phosphorylation and signaling and elicits tumor cell killing via ADCC in vitro and in vivo. In primary human immune cells, CDX-0168 treatment induces potent release of pro-inflammatory cytokines and chemokines from dendritic cells, monocytes and macrophages through an Fc receptor-dependent mechanism and enhanced T cell activation in mixed lymphocyte reactions. Axl inhibition may further enhance antitumor activity associated with PD-(L)1 blockade. To this end, we generated a tetravalent bispecific Axl x PD-L1 antibody combining CDX-0168 with a potent anti-PD-L1 mAb (9H9) using an IgG-scFv format. The bispecific antibody elicits greater cytokine release and T cell activation in vitro than the combination of the parental antibodies, while maintaining robust Axl and PD-L1 blockade.ConclusionsAdditional studies investigating simultaneous blockade of the Axl and PD-L1 pathways with other agents may further exploit the potential for this novel anti-cancer therapeutic approach.

scholarly journals Competitive Inhibition In Vivo and Skewing of the T Cell Repertoire of Antigen-Specific CTL Priming by an Anti-Peptide-MHC Monoclonal Antibody

2001 ◽  
Vol 167 (2) ◽  
pp. 699-707 ◽  
Author(s):  
Doo Hyun Chung ◽  
Igor M. Belyakov ◽  
Michael A. Derby ◽  
Jian Wang ◽  
Lisa F. Boyd ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cell ◽  
Competitive Inhibition ◽  
T Cell Repertoire ◽  
Cell Repertoire
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