Differential lysis of tumor target cells displayed by lymphokine activated killer (LAK) cell clones

1992 ◽  
Vol 10 (3) ◽  
pp. 190-195 ◽  
Author(s):  
Pamela Bean ◽  
Ravin Agah ◽  
Amilabha Mazumder
Keyword(s):  
Target Cells ◽  
Tumor Target ◽  
Lak Cell ◽  
Cell Clones ◽  
Differential Lysis

Evaluation of the MTT and SRB assays for testing LAK cell-mediated growth inhibition of various adherent and non-adherent tumor target cells

1994 ◽  
Vol 170 (2) ◽  
pp. 269-271 ◽  
Author(s):  
Frank Garbin ◽  
Klaus Eckert ◽  
H. Rainer Maurer
Keyword(s):  
Growth Inhibition ◽  
Target Cells ◽  
Tumor Target ◽  
Lak Cell

Assignment of human natural killer (NK)-like cells to the T cell lineage. Single allospecific T cell clones lyse specific or NK-sensitive target cells via distinct recognition structures

1984 ◽  
Vol 14 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Alessandro Moretta ◽  
Giuseppe Pantaleo ◽  
Maria Cristina Mingari ◽  
Giovanni Melioli ◽  
Lorenzo Moretta ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lineage ◽  
Target Cells ◽  
T Cell Clones ◽  
Cell Clones

scholarly journals Specificity studies on cytolytic T lymphocytes directed against murine leukemia virus-induced tumors. Analysis of monoclonal cytolytic T lymphocytes.

1982 ◽  
Vol 155 (4) ◽  
pp. 1050-1062 ◽  
Author(s):  
F Plata
Keyword(s):  
T Lymphocytes ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Tumor Target ◽  
Induced Tumors ◽  
Definition Of ◽  
Leukemia Viruses ◽  
Murine Leukemia

The specificities of cloned cytolytic T lymphocytes (CTL) were studied for the analysis of CTL populations generated against murine leukemia viruses (MuLV) in H-2 congenic BALB/c (H-2d) and BALB.B (H-2b) mice. In particular, CTL generated in response to tumors induced by Gross MuLV and Friend MuLV were studied; these tumors expressed virus-induced antigens that do not cross-react and that can be distinguished from each other. The systematic study of 92 CTL clones clearly indicated that MuLV-immune CTL were highly heterogeneous with respect to both the intensities of target cell lysis that they mediated and to their specificity of recognition of MuLV-induced tumor target cells. Various categories of CTL clones were identified, ranging from CTL clones tht were tightly H-2 restricted and specific for the immunizing tumor to CTL clones that displayed no discernible patterns of specificity and that attacked a large number of different target cells. In addition, the surface markers of these cloned CTL were defined, and the best conditions for their prolonged maintenance in culture were determined. The present data indicate that future efforts in the definition of target antigens recognized by tumor-specific CTL should be performed with monoclonal lymphocytes.

scholarly journals Listeria monocytogenes-reactive T lymphocyte clones with cytolytic activity against infected target cells.

1986 ◽  
Vol 164 (1) ◽  
pp. 363-368 ◽  
Author(s):  
S H Kaufmann ◽  
E Hug ◽  
G De Libero
Keyword(s):  
T Cells ◽  
Listeria Monocytogenes ◽  
T Lymphocyte ◽  
Cytotoxic T Cells ◽  
Cytolytic Activity ◽  
Target Cells ◽  
Intracellular Bacteria ◽  
Spleen Cells ◽  
Ifn Gamma ◽  
Cell Clones

Lyt-2+ T cell clones were established from Listeria monocytogenes-infected mice. The clones secreted IFN-gamma after stimulation with spleen cells from L. monocytogenes-infected mice plus IL-2. Spleen cells from normal mice were not stimulatory. Furthermore, cloned T cells lysed L. monocytogenes-infected macrophages. Cytolysis was antigen-specific and H-2K-restricted. These findings suggest a role for specific cytotoxic T cells in the immune response to intracellular bacteria.

scholarly journals 894 The bispecific innate cell engagers AFM13 (CD30/CD16A) and AFM24 (EGFR/CD16A) increase the fraction of tumor target-responsive NK cells and boost serial killing

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A938-A938
Author(s):  
Chiara Zambarda ◽  
Karolin Guldevall ◽  
Chiara Zambarda ◽  
Karolin Guldevall ◽  
Christian Breunig ◽  
...  
Keyword(s):  
Nk Cells ◽  
Single Cell ◽  
Tumor Cells ◽  
Cell Biology ◽  
Nk Cell ◽  
Biological Evaluation ◽  
Target Cells ◽  
List Type ◽  
Tumor Target ◽  
Serial Killing

BackgroundThe use of bispecific natural killer (NK) cell engagers has emerged as a successful strategy for immune cell activation and killing of tumor cells through antibody-dependent cellular cytotoxicity (ADCC). Among these, tetravalent, bispecific innate cell engagers (ICE®) with specificity for the activating receptor CD16A selectively triggering innate responses from NK cells or macrophages represent the most clinically advanced concept. The CD30/CD16A specific ICE® AFM13, has shown efficacy in patients with CD30+ lymphomas as monotherapy1 and combination therapy with check-point inhibitors2 and most recently in combination with adoptive NK cell therapy.3 The EGFR/CD16A specific ICE® AFM24, targeting a variety of solid tumors like colorectal, or lung cancer with a unique mode of action independent of EGFR signaling inhibition, is currently evaluated in an ongoing Ph1/2a clinical study.MethodsWe used a microchip-based screening with single cell resolution4 to elucidate the dynamic responses of individual NK cells towards tumor target cells upon treatment with AFM13 or AFM24.ResultsWe found that AFM13 and AFM24 mediated potent activation of NK cells, leading to increased responsive cytotoxic NK cells and significantly increased the number of NK cells that exerted engagement with multiple target cells rendering these NK cells serial killers. Strikingly, bispecific ICE® molecules triggered stronger cytotoxic responses compared to monoclonal antibodies. One suggested strategy to boost killing by NK cells is to use molecular inhibitors or protein constructs that prevent shedding of CD16.5 However, previous results have shown that this can lead to impaired detachment from target cells, reducing the capacity for an individual NK cell to form serial contacts to target cells.6 We observed that the elevated NK cell killing induced by ICE® molecules was largely conserved when cells were treated with the shedding inhibitor Batimastat. Analysis of the functional dynamics of NK cells revealed that inhibition of CD16 shedding prevented NK cell detachment from target cells, resulting in cell cluster formation. This might strongly impact targeting of distant tumor cells by an individual NK cell thus limiting its anti-tumoral activity.ConclusionsIn conclusion, we show that both AFM13 and AFM24 increase the fraction of tumor-target responsive NK cells and boost serial killing of target cells by individual NK cells. Based on these data, ICE® molecules can be characterized as potent anti-tumoral agents leveraging the enormous potential of NK cells while maintaining crucial features of NK cell biology.AcknowledgementsWe thank members of the Önfelt lab for their valuable help and feedback.ReferencesSawas A, Elgedawe H, Vlad G, Lipschitz M, Chen P-H, Rodig SJ, et al. Clinical and biological evaluation of the novel CD30/CD16A tetravalent bispecific antibody (AFM13) in relapsed or refractory CD30-positive lymphoma with cutaneous presentation: a biomarker phase Ib/IIa study (NCT03192202). Blood 2018;132(Supplement 1):2908–2908.Bartlett NL, Herrera AF, Domingo-Domenech E, Mehta A, Forero-Torres A, Garcia-Sanz R, et al. A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma. Blood 2020. Blood 2020;136(21):2401–2409.Kerbauy LN, Marin ND, Kaplan M, Banerjee PP, Berrien-Elliott MM, Becker-Hapak M, et al. Combining AFM13, a bispecific CD30/CD16 antibody, with cytokine-activated blood and cord blood–derived NK cells facilitates CAR-like responses against CD30 + malignancies. Clin Cancer Res Epub 2021.Guldevall K, Brandt L, Forslund E, Olofsson K, Frisk TW, Olofsson PE, et al. Microchip screening platform for single cell assessment of NK cell cytotoxicity. Front Immunol 2016;7:119.Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, et al. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood 2013;121(18):3599–608.Srpan K, Ambrose A, Karampatzakis A, Saeed M, Cartwright ANR, Guldevall K, et al. Shedding of CD16 disassembles the NK cell immune synapse and boosts serial engagement of target cells. J Cell Biol 2018;217(9):3267–83.Ethics ApprovalThis work was performed with NK cells from healthy anonymous blood donors, which requires no ethical permit according to local regulations.

scholarly journals Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor using cyclosporine-induced syngeneic graft-versus-host disease in the rat

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 1165-1171 ◽  
Author(s):  
RB Geller ◽  
AH Esa ◽  
WE Beschorner ◽  
CG Frondoza ◽  
GW Santos ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Clinical Signs ◽  
Class Ii ◽  
Target Cells ◽  
Tumor Target ◽  
Host Disease ◽  
Class Ii Mhc ◽  
Mhc Antigen ◽  
Nylon Wool

Abstract Lethally irradiated LouM rats reconstituted with syngeneic bone marrow and then treated with cyclosporine (CsA) for 40 consecutive days following transplant developed a graft-v-host disease (GVHD)-like syndrome after CsA cessation. This model of GVHD was used to define and characterize a graft-v-tumor (GVT) effect against a syngeneic plasmacytoma CRL1662 cell line which expresses class II major histocompatibility (MHC) antigen (Ia). Nylon wool-nonadherent spleen cells from animals who developed syngeneic GVHD were capable of significant lysis against chromium-labeled tumor target cells in a four- hour chromium released cell mediated lympholysis assay; maximum lysis occurred five days following cessation of CsA when clinical signs first appeared. Cytolytic activity declined to baseline as GVHD symptoms resolved. Fractionation of splenocytes into lymphocyte subsets demonstrated that cytolytic lymphocytes (CTLs) of the OX8 phenotype (non-helper T) were capable of significant lysis against tumor target cells. Lysis of tumor cells was blocked by preincubation with monoclonal antibodies (MoAb) specific for the rat anti-class II MHC antigen but not with MoAb against class I. Incubation of tumor cells with gamma-interferon increased expression of tumor class II MHC antigens and significantly increased their susceptibility to lysis by nylon wool-nonadherent splenocytes from animals with syngeneic GVHD. These studies have demonstrated an in vitro GVT of syngeneic GVHD against an Ia-bearing tumor; the effector cell is a CTL of the OX8 phenotype specific for the class II MHC antigen.

Macrophage Antitumor Activity Induced by the Antigenic Lymphoma L5178Y/DTIC Subline

1982 ◽  
Vol 68 (5) ◽  
pp. 365-371 ◽  
Author(s):  
Ornella Marelli ◽  
Alberto Mantovani ◽  
Paola Franco ◽  
Angelo Nicotin
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Peritoneal Macrophages ◽  
Leukemic Cells ◽  
Target Cells ◽  
Tumor Target ◽  
Growth Inhibitory

Murine leukemic cells, after in vivo treatment with antineoplastic drugs, have been shown to express new antigenic specificities that were not detectable on parental cells and that were heritable after the withdrawal of drug treatment. A study was conducted of macrophage antitumor activity triggered by LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. In vitro non-specific inhibition of tumor cell growth was exhibited by spleen and peritoneal macrophages from mice previously challenged with viable LY/DTIC. Peritoneal macrophages from LY/DTIC immune animals showed moderate, although significant lytic activity against unrelated tumor target cells. Supernatants from mixed lymphocyte-tumor cell cultures, in which LY/DTIC immune lymphocytes and LY/DTIC tumor cells had been cultured, rendered normal macrophages non-specifically growth inhibitory for tumor cells.

scholarly journals Functional characterization of a stable, noncytolytic stage of macrophage activation in tumors.

1977 ◽  
Vol 146 (6) ◽  
pp. 1511-1520 ◽  
Author(s):  
S W Russell ◽  
W F Doe ◽  
A T McIntosh
Keyword(s):  
Macrophage Activation ◽  
Functional Characterization ◽  
Cytolytic Activity ◽  
Target Cells ◽  
Tumor Target ◽  
Total Absence

The state in which macrophages (Mphi) from regressing Moloney sarcomas could kill tumor target cells was a highly labile one which decayed rapidly in vitro. Thereafter, regressor Mphi were noncytolytic. Mphi from several different progressing sarcomas failed to kill, even when challenged with target cells immediately after explantation. Similarly, thioglycollate-induced peritoneal Mphi (TG-Mphi) did not kill. Noncytolygic Mphi derived either from progressing sarcomas or from long-term (up to 96 h) cultures of regressor Mphi were exquisitely sensitive to stimulation by bacterial lipopolysaccharide (LPS); picogram/milliliter amounts induced killing. Similar concentrations of LPS had no demonstrable effect on TG-Mphi. Thus, tumor Mphi generally appeared to have been primed in vivo, with those in regressing sarcomas having additionally acquired cytolytic activity. Inability of progressor Mphi to kill apparently stemmed from lack of, or failure to respond to, the signal needed in vivo to trigger cytolytic activity, rather than the total absence of activation.

scholarly journals Cell-type-specific cytotoxicity of anti-CD4 and anti-CD8 ricin immunotoxins against human alloreactive T-cell clones

Blood ◽  
1989 ◽  
Vol 74 (7) ◽  
pp. 2445-2454 ◽  
Author(s):  
FM Uckun ◽  
DE Myers ◽  
JA Ledbetter ◽  
SL Wee ◽  
DA Vallera
Keyword(s):  
T Cell ◽  
Cell Subset ◽  
Target Cells ◽  
Cell Type ◽  
T Cell Clones ◽  
First Order ◽  
Cell Clones ◽  
T Cell Clone ◽  
Cell Type Specific ◽  
Alloreactive T Cell

Abstract Potent T-cell subset-directed immunotoxins (ITs) were generated by conjugating the anti-CD4 monoclonal antibody (MoAb) G17–2 and the anti- CD8 MoAb G10.1 to the ribosome-inhibitory protein, ricin. The cell-type- specific cytotoxicities of the generated ITs were evaluated at the clonal level using human alloreactive T-cell clones. The kinetics of anti-CD4 ricin-induced inactivation of protein synthesis in target CD4+ cloned T-cells was first order with no detectable lag period and a maximum rate of 0.07 logs per hour (t10 = 13.6 hours; first-order rate constant/K = 0.17 hr-1). The alloantigen specific lytic function of the CD4+ cytolytic T-cell clone JMAC28 was acutely sensitive to anti-CD4 ricin, and no residual lytic activity against allogeneic targets was detectable 24 hours after treatment with as little as 0.5 mmol/L anti- CD4 ricin. Notably, both anti-CD4 ricin and anti-CD8 ricin elicited a selective and dose-dependent inhibition of clonal proliferation of target T-cell clones with a maximum kill of greater than 3 logs at 5 nmol/L. No significant “bystander effects” were observed for non-target cells. Bone marrow progenitor cells CFU-GM, BFU-E, and CFU-GEMM were only minimally affected by either IT. We conclude that these ITs show considerable potential for effective depletion of T-cell subpopulations from allogeneic donor marrow grafts for clinical graft-versus-host disease (GVHD) prophylaxis.

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