Studies on antigenic competition. Efforts to identify the cellular basis of competition using a cell transfer system

BackgroundAdoptive T-cell transfer has become an attractive therapeutic approach for hematological malignancies but shows poor activity against large and heterogeneous solid tumors. Interleukin-12 (IL-12) exhibits potent antitumor efficacy against solid tumors, but its clinical application has been stalled because of toxicity. Here, we aimed to develop a safe approach to IL-12 T-cell therapy for eliminating large solid tumors.MethodsWe generated a cell membrane-anchored IL-12 (aIL12), a tumor-targeted IL-12 (ttIL12), and a cell membrane-anchored and ttIL-12 (attIL12) and a cell membrane-anchored and tumor-targeted ttIL-12 (attIL12) armed T cells, chimeric antigen receptor-T cells, and T cell receptor-T (TCR-T) cells with each. We compared the safety and efficacy of these armed T cells in treating osteosarcoma patient-derived xenograft tumors and mouse melanoma tumors after intravenous infusions of the armed T cells.ResultsattIL12-T cell infusion showed remarkable antitumor efficacy in human and mouse large solid tumor models. Mechanistically, attIL12-T cells targeted tumor cells expressing cell-surface vimentin, enriching effector T cell and interferon γ production in tumors, which in turn stimulates dendritic cell maturation for activating secondary T-cell responses and tumor antigen spreading. Both attIL12- and aIL12-T-cell transfer eliminated peripheral cytokine release and the associated toxic effects.ConclusionsThis novel approach sheds light on the safe application of IL-12-based T-cell therapy for large and heterogeneous solid tumors.

Download Full-text

IMMUNE RESPONSES AGAINST NATIVE AND CHEMICALLY MODIFIED ALBUMINS IN MICE

Journal of Experimental Medicine ◽

10.1084/jem.136.6.1616 ◽

1972 ◽

Vol 136 (6) ◽

pp. 1616-1630 ◽

Cited By ~ 52

Author(s):

Volker Schirrmacher ◽

Hans Wigzell

Keyword(s):

T Cells ◽

Bovine Serum Albumin ◽

Immune Responses ◽

Immune Cells ◽

Reduction Factor ◽

Helper T Cells ◽

Transfer System ◽

Cell Transfer ◽

Chemically Modified ◽

Pronounced Reduction

Immune cells induced by bovine serum albumin (BSA) and its methylated derivative (MBSA) have been compared in a cooperative cell transfer system for their content of BSA-specific antibody-forming cell precursors (AFCP, B) and BSA-specific helper (T) cells. When MBSA immune cells were transferred together with hapten-primed cells into recipient mice which were stimulated by a hapten-BSA conjugate, their cooperative secondary anti-hapten response was as good as in case of transferred BSA immune cells. Their secondary anti-BSA response, however, was markedly reduced (reduction factor > 30). Hapten-MBSA conjugates had the same capacity to react with BSA-specific helper cells in the cooperative secondary anti-hapten response as hapten-BSA conjugates but had a reduced ability to react with BSA-specific AFCP cells. In spite of the pronounced reduction of the B cell response, MBSA had the same threshold dose as BSA for activating BSA-specific T cells. These data suggest that B and T cells recognize different epitopes on the BSA molecule, only those recognized by B cells being affected by the methylation procedure.

Download Full-text

UHV-liquid cell transfer system for Auger electron spectroscopy on electrodes

Surface and Interface Analysis ◽

10.1002/sia.1374 ◽

2002 ◽

Vol 34 (1) ◽

pp. 623-627 ◽

Cited By ~ 6

Author(s):

F. Reniers ◽

V. Rooryck ◽

S. Pace ◽

C. Buess-Herman

Keyword(s):

Auger Electron Spectroscopy ◽

Electron Spectroscopy ◽

Auger Electron ◽

Transfer System ◽

Cell Transfer ◽

Liquid Cell

Download Full-text

Retrotransposition and Cell-to-Cell Transfer of Foamy Viruses

Journal of Virology ◽

10.1128/jvi.77.21.11855-11858.2003 ◽

2003 ◽

Vol 77 (21) ◽

pp. 11855-11858 ◽

Cited By ~ 16

Author(s):

Martin Heinkelein ◽

Matthias Rammling ◽

Thomas Juretzek ◽

Dirk Lindemann ◽

Axel Rethwilm

Keyword(s):

High Efficiency ◽

Transmembrane Protein ◽

Foamy Virus ◽

Marker Gene ◽

Cell Transfer ◽

Remarkable Feature ◽

Initial Report ◽

A Cell ◽

A Minor ◽

Cell To Cell Transfer

ABSTRACT A remarkable feature of the prototype foamy virus (PFV) replication pathway has been reported to consist of the ability to retrotranspose intracellularly with high efficiency (M. Heinkelein, T. Pietschmann, G. Jármy, M. Dressler, H. Imrich, J. Thurow, D. Lindemann, M. Bock, A. Moebes, J. Roy, O. Herchenröder, and A. Rethwilm, EMBO J. 19:3436-3345, 2000). PFV intracellular retrotransposition (IRT) was reported to be enhanced by coexpression of fusion-defective envelope protein. To investigate the possibility of cell-to-cell transfer of PFV genomes, which could mimic IRT, we performed cocultivation experiments with cells transfected with an IRT-competent and marker gene-expressing PFV vector together with cells expressing a different marker and measured cells positive for both markers. The findings corroborated the initial report on IRT of Env-deficient PFV. Furthermore, they indicated that viral cores that have incorporated fusion-deficient Env can be transferred from cell to cell in a cell type-specific manor. One possible explanation consists of a minor alternative cleavage site in Env that can be used to expose the fusion peptide of the Env transmembrane protein, which appears to be required for virus uptake.

Download Full-text

Cellular Basis of Life

Examining the Causal Relationship Between Genes, Epigenetics, and Human Health - Advances in Bioinformatics and Biomedical Engineering ◽

10.4018/978-1-5225-8066-9.ch003 ◽

2019 ◽

pp. 56-91

Keyword(s):

Raw Materials ◽

Single Cells ◽

The Body ◽

Tissue Fluid ◽

Single System ◽

System Communication ◽

Cellular Basis ◽

A Cell ◽

Maintenance Activities ◽

Multiple Cells

To qualify as living, units of life called cells must be identifiable, distinct, and demonstrate most or all the qualities of life. Cells tremendously vary in size from about 0.5-500 micrometers. The smallest known single cells are those of bacteria while most higher organisms have multiple cells differentiated and functioning together as a single system. Communication in cells involves cell signaling, reception, transduction, and response. Signals received at the surface of the cell from other cells, or from blood or tissue fluid must be transferred to various parts of the cell and a cell response initiated. Cells actively take in raw materials which they use to function and perform maintenance activities. Collectively these activities are called cellular metabolism catalysed by enzymes. To avoid chaos in the body, cells maintain control of what reactions are needed all the time, needed only certain times or needed very rarely. This chapter explores the cellular basis of life.

Download Full-text

Establishment of a single-step hybridoma cloning protocol using an automated cell transfer system: comparison with limiting dilution

Journal of Immunological Methods ◽

10.1016/0022-1759(94)00274-z ◽

1995 ◽

Vol 179 (1) ◽

pp. 71-76 ◽

Cited By ~ 20

Author(s):

Konstantin Wewetzer ◽

Bernd Seilheimer

Keyword(s):

Single Step ◽

Transfer System ◽

Cell Transfer ◽

Limiting Dilution

Download Full-text

The cellular basis of allograft rejection in vivo. II. The nature of memory cells mediating second set heart graft rejection.

Journal of Experimental Medicine ◽

10.1084/jem.148.4.890 ◽

1978 ◽

Vol 148 (4) ◽

pp. 890-902 ◽

Cited By ~ 50

Author(s):

B M Hall ◽

S Dorsch ◽

B Roser

Keyword(s):

Graft Rejection ◽

Allograft Rejection ◽

Lymphoid Tissue ◽

Fold Increase ◽

Transfer System ◽

Memory Cells ◽

Cellular Basis ◽

Heart Graft ◽

Histocompatibility Complex

An adoptive transfer system was used to study the cellular basis of memory in animals immunized by grafting with major histocompatibility complex incompatible tissue. Memory was characterised by a large (greater than 100 fold) increase in the potency of lymphocytes to precure graft rejection. This increase in potency endured for at least 1 yr after sensitization. The memory cells were shown to be Ig-- small lymphocytes which were long lived and which did not recirculate from blood to lymph in normal recipients although they did home to lymphoid tissue from which they could be recovered several months later. The thymus was not required either for the generation of memory cells or their maintenance. Cells carrying memory for alloantibody synthesis did recirculate normally but alloantibody synthesis was shown not to be required for rejection.

Download Full-text

QUANTITATIVE STUDIES OF THE ADOPTIVE IMMUNOLOGICAL MEMORY IN MICE

Journal of Experimental Medicine ◽

10.1084/jem.125.2.199 ◽

1967 ◽

Vol 125 (2) ◽

pp. 199-211 ◽

Cited By ~ 45

Author(s):

Franco Celada

Keyword(s):

Half Life ◽

Immunological Memory ◽

Transfer System ◽

Cell Transfer ◽

Mouse Spleen Cell ◽

Stem Cell Line ◽

Anamnestic Response ◽

Daughter Cells ◽

Quantitative Studies ◽

Two Phases

A calibrated cell transfer system allows detection of the anamnestic response to albumin without interference from the host's immune machinery; it was used to study the immunological memory of mouse spleen cell populations. The secondary antibody-forming capacity of the transferred cells was measured by challenging them at periods up to 6 months after transfer. The peak levels attained show a declining pattern in two phases: during the first month with a half-life of 15 days; thereafter, with a half-life of 100 days. The corresponding half-lives of the cellular memory are 26 and 190 days. In the light of these and of radioinactivation data, immunological memory is defined as the persistence of a specifically determined stem cell line, along which the information necessary to give rise to an antibody-forming cell population is transmitted from mother to daughter cells.

Download Full-text