The in vitro induction of T cells which mediate delayed-type hypersensitivity toward horse red blood cells

AbstractCheckpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12. This leads to robust, antigen-specific T-cell expansion, memory formation, additional immune activation, tumor control, and antigen spreading in tumor models in vivo. The presence of 4-1BBL and IL-12 induces minimal toxicities due to restriction to the vasculature and spleen. The allogeneic aAPC, RTX-321, comprised of human leukocyte antigen-A*02:01 presenting the human papilloma virus (HPV) peptide HPV16 E711-19, 4-1BBL, and IL-12 on the surface, activates HPV-specific T cells and promotes effector function in vitro. Thus, RTX-321 is a potential ‘off-the-shelf’ in vivo cellular immunotherapy for treating HPV + cancers, including cervical and head/neck cancers.

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SUPPRESSION OF “IN VITRO” ANTIBODY SYNTHESIS BY A T CELL PRODUCT. ITS RELATION WITH THE Fc RECEPTOR OF ACTIVATED T CELLS11This work was supported by grants from INSERM and CNRS.,22Abbreviations used in this paper: ATC: activated T cells, DNP-AE-DEXTRAN: dinitrophenylated-aminoethyl-dextran, EAIgG: sheep erythrocytes sensitized with rabbit anti-Forssman IgG, IBF: Immunoglobulin Binding Factor, PFC: Plaque forming cells, SRBC: sheep red blood cells, TRF: T cell replacing factor.

Leukocyte Membrane Determinants Regulating Immune Reactivity ◽

10.1016/b978-0-12-233750-5.50058-0 ◽

1976 ◽

pp. 331-338 ◽

Cited By ~ 2

Author(s):

Wolf H. FRIDMAN ◽

Catherine NEAUPORT-SAUTES ◽

Annick GUIMEZANES ◽

Roland H. GISLER

Keyword(s):

T Cells ◽

T Cell ◽

Red Blood Cells ◽

Blood Cells ◽

Activated T Cells ◽

Sheep Erythrocytes ◽

Cell Product ◽

Binding Factor ◽

Immunoglobulin Binding

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RESTORATION OF CELL-MEDIATED IMMUNITY TO ANIMALS BLOCKED BY A HUMORAL RESPONSE

Journal of Experimental Medicine ◽

10.1084/jem.140.3.865 ◽

1974 ◽

Vol 140 (3) ◽

pp. 865-870 ◽

Cited By ~ 14

Author(s):

George B. MacKaness ◽

Philippe H. Lagrange

Keyword(s):

T Cells ◽

Antibody Response ◽

Red Blood Cells ◽

Blood Cells ◽

Humoral Response ◽

Delayed Type Hypersensitivity ◽

Cell Mediated Immunity ◽

Continuous Exposure ◽

Long Period ◽

Blocking Factors

The T cells which mediate delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) are blocked by a normal humoral response and cannot be made to function by further immunization. They can be rescued to some extent by treatment with immunopotentiating agents such as cyclophosphamide (CY) which suppresses the antibody response selectively, or by BCG which interferes with the action of serum blocking factors. These two agents together can restore cell-mediated immunity completely, but a further antigenic stimulus is needed to reestablish DTH in mice blocked by a long period of continuous exposure to SRBC.

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In vitro transfusion of red blood cells results in decreased cytokine production by human T cells

Journal of Trauma and Acute Care Surgery ◽

10.1097/ta.0000000000000330 ◽

2014 ◽

Vol 77 (2) ◽

pp. 198-201 ◽

Cited By ~ 7

Author(s):

Kristin Long ◽

Jerold Woodward ◽

Levi Procter ◽

Marty Ward ◽

Cindy Meier ◽

...

Keyword(s):

T Cells ◽

Red Blood Cells ◽

Blood Cells ◽

Cytokine Production ◽

Human T Cells

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Virus-replicating T cells in the immune response of mice. I. Virus plaque assay of the lymphocytes reactive to sheep erythrocytes.

Journal of Experimental Medicine ◽

10.1084/jem.145.2.390 ◽

1977 ◽

Vol 145 (2) ◽

pp. 390-404 ◽

Cited By ~ 5

Author(s):

N Minato ◽

Y Katsura

Keyword(s):

Immune Response ◽

T Cells ◽

Red Blood Cells ◽

Blood Cells ◽

Cultured Cells ◽

Plaque Assay ◽

Delayed Type Hypersensitivity ◽

Mouse Serum ◽

Spleen Cells ◽

Helper Activity

Virus plaque-forming cell assay with vesicular stomatitis virus (VSV), which had been originally introduced by Bloom and his colleagues as a tool for the enumeration of activated lymphocytes, was first applied to the immune response of mice to a widely used antigen, i.e. sheep red blood cells (SRBC). When spleen cells taken from mice previously primed with SRBC were cultured in the presence of the antigen, lymphocytes capable of replicating VSV (antigen-induced virus plaque-forming cells, Ag-V-PFC) were generated in the culture. They seemed to appear as early as 1 day of culture, and the peak was attained by the 2nd day. Most of Ag-V-PFC belonged to T-cell population, since 80-90% of Ag-V-PFC was killed by the treatment of cultured cells with anti-thymocyte serum plus complement. In vitro generation of Ag-V-PFC seemed to be highly cross-reactive (about 40%) with a related antigen (horse red blood cells). Ag-V-PFC detected in the present experiment may not represent helper T cells, effector T cells, or their precursors because of the following: (a) The generation of Ag-V-PFC was completely suppressed by the addition of anti-SRBC mouse serum in the culture, though the helper activity was apparently augmented by the same treatment. (b) Development of Ag-V-PFC was almost completely suppressed by the pretreatment of mice with cyclophosphamide 2 days before immunization, by which delayed-type hypersensitivity (DTH) was markedly augmented. (c) After the immunization of mice, Ag-V-PFC began to develop just when the level of DTH declined, at which point helper activity of the spleen cells also diminished. A possible role of Ag-V-PFC in the immune response was discussed.

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