Chimeric antigen receptor

Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins, such as surface proteins on cancer cells, that is added to immune cells for immunotherapy strategies such as directing T cells to fight cancer.

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CARs are recombinant protein molecules that cause cell activation upon encountering the target antigen. The antigen-recognition domain of a CAR is usually derived from monoclonal antibody sequences.Cellsequences. Cell therapies being used or in development for treating cancer or autoimmune diseases use T cells or regulatory T cells (Tregs) respectively. CAR-T cells are engineered T cells and CAR-Treg cells are engineered Tregs.

Jude Gomila
Jude Gomila approved a suggestion from Golden's AI on 19 Mar, 2019
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CARs are recombinant protein molecules that cause cell activation upon encountering the target antigen. The antigen-recognition domain of a CAR is usually derived from monoclonal antibody sequences.Cell therapiesCell therapies being used or in development for treating cancer or autoimmune diseases use T cells or regulatory T cells (Tregs) respectively. CAR-T cells are engineered T cells and CAR-Treg cells are engineered Tregs.

Edits on 18 Mar, 2019
Meredith Hanel
Meredith Hanel edited on 18 Mar, 2019
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Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins, such as surface proteins on cancer cells, that is added to immune cells for immunotherapyimmunotherapy strategies such as directing T cells to fight cancer.

Edits on 2 Mar, 2019
Jude Gomila
Jude Gomila approved a suggestion from Golden's AI on 2 Mar, 2019
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The first CAR-T treatment was approved by the FDA in 2017 and there are several in clinical trials. CAR-T has been successful in treating hematological malignancies. US FDA approved CAR-T therapies include CD19-targeting CAR-T cells, tisagenlecleucel (Kymriah-Novartis) in leukemia and lymphoma and axicabtagene ciloleucel (Yescarta – Kite) in lymphoma. Challenges to CAR-T including toxicity due to attacking non-cancer cells, "clonal escape" due to diversity of cancer cellscancer cells, dosing, immunosuppression (turning off) of the T-cells, and T-cell apoptosis (cell death).

Jude Gomila
Jude Gomila approved a suggestion from Golden's AI on 2 Mar, 2019
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Allogeneic or universal cell therapy products, also called off-the-shelf cell therapy products would allow a broader implementation of these cell therapies. One method being researched is to derive natural killer (NK) cells from induced pluripotent stem cells (iPS) cells and engineer iPS cell-derived NK cells to target and kill cancer cellcancer cell similarly to CAR-T cells.

Jude Gomila
Jude Gomila approved a suggestion from Golden's AI on 2 Mar, 2019
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The first CAR-T treatment was approved by the FDA in 2017 and there are several in clinical trials. CAR-T has been successful in treating hematological malignancies. US FDA approved CAR-T therapies include CD19-targeting CAR-T cells, tisagenlecleucel (Kymriah-Novartis) in leukemia and lymphoma and axicabtagene ciloleucel (Yescarta – Kite) in lymphoma. Challenges to CAR-T including toxicity due to attacking non-cancer cells, "clonal escape" due to diversity of cancer cells, dosing, immunosuppression (turning off) of the T-cells, and T-cell apoptosis (cell deathcell death).

Edits on 28 Feb, 2019
Meredith Hanel
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Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins on cancer cells that is added to immune cells, for immunotherapy strategies such as T cells.directing T cells modified with a chimeric antigen receptor (CAR), called CAR-T cells, are designed to find and killfight cancer cells that carry the protein recognized by the receptor.

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CARs are recombinant protein molecules that cause cell activation upon encountering the target antigen. The antigen-recognition domain of a CAR is usually derived from monoclonal antibody sequences.Cell therapies being used or in development for treating cancer or autoimmune diseases use T cells or regulatory T cells (Tregs) respectively. CAR-T cells are engineered T cells and CAR-Treg cells are engineered Tregs.

ChimericT cells modified with a chimeric antigen receptorsreceptor (CARsCAR), called CAR-T cells, are recombinantdesigned to find and kill cancer cells that carry the protein molecules that cause cell activation uponrecognized encounteringby the target antigen. The antigen-recognition domain of a CAR is usually derived from monoclonal antibody sequencesreceptor. This region interacts with tumor cell surface proteins and signaling motifs in the intracellular portion of the CAR ensure cell activation. The interaction occurs in a major histocompatibility complex (MHC)-unrestricted manner.This means the interaction does not require MHC compatibility between effector and target cell. This is important because tumors often lose MHC expression as a mechanism of evading detection by endogenous T cells.

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Synthetic Biology Approaches

Improved tumor recognition and specificity has been shown by incorporating the synNotch transcriptional receptor which creates a two antigen tumor recognition circuit. One antigen binds synNotch and primes CAR expression and a second antigen binds CAR to activate the T cell. This system is being used by Cell Design Labs to develop CAR-T therapies.

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Meredith Hanel
Meredith Hanel edited on 28 Feb, 2019
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The first CAR-T treatment was approved by the FDA in 2017 and there are several in clinical trials. CAR-T has been successful in treating hematological malignancies. US FDA approved CAR-T therapies include CD19-targeting CAR-T cells, tisagenlecleucel (Kymriah-Novartis) in leukemia and lymphoma and axicabtagene ciloleucel (Yescarta – Kite) in lymphoma. Challenges to CAR-T including toxicity due to attacking non-cancer cells, "clonal escape" due to diversity of cancer cells, dosing, immunosuppression (turning off) of the T-cells, and T-cell apoptosis (cell death).

Treating solid tumors with CAR-T faces challenges including a lack of truly tumor-specific target antigens. The immunosuppressiveness of the tumor microenvironment (TME) of solid tumors also prevents effective anti-tumor immune responses. Components of the immunosuppressive TME contains includes physical barriers, such as a dense extracellular matrix; dysfunctional epithelial cells; metabolic checkpoints, such as hypoxia and immunological barriers, such as immunosuppressive cytokines/molecules and immunosuppressive immune cells.

Meredith Hanel
Meredith Hanel edited on 28 Feb, 2019
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To generate CAR-T cells for therapy a CAR-encoding DNA cassette is transduced by retroviral delivery into patient peripheral blood leukocytes from a cancer patient. Transduced cells are expanded and reinfused back into the patient. The introduced DNA sequences for the tumor associated antigens are ideally only expressed on tumor cells.

Allogeneic or universal cell therapy products, also called off-the-shelf cell therapy products would allow a broader implementation of these cell therapies. One method being researched is to derive natural killer (NK) cells from induced pluripotent stem cells (iPS) cells and engineer iPS cell-derived NK cells to target and kill cancer cell similarly to CAR-T cells.

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CAR-T Companies: The Meteoric Rise Of Cellular Immunotherapies

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Meredith Hanel
Meredith Hanel edited on 27 Feb, 2019
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Chimeric antigen receptors (CARs) are recombinant protein molecules that cause cell activation upon encountering the target antigen. The antigen-recognition domain of a CAR is usually derived from monoclonal antibody sequences. This region interacts with tumor cell surface proteins and signaling motifs in the intracellular portion of the CAR ensure cell activation. The interaction occurs in a major histocompatibility complex (MHC)-unrestricted manner.This means the interaction does not require MHC compatibility between effector and target cell. This is important because tumors often lose MHC expression as a mechanism of evading detection by endogenous T cells.

Meredith Hanel
Meredith Hanel edited on 27 Feb, 2019
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Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins on cancer cells that is added to immune cells, such as T cells. T cells modified with a chimeric antigen receptor (CAR), generatingcalled CAR-T cells with, theare potentialdesigned to find and kill cancer cells that carry the protein recognized by the receptor.

Meredith Hanel
Meredith Hanel edited on 27 Feb, 2019
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Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins on cancer cells that is added to T cells, generating CAR-T cells with the potential to find and kill cancer cells that carry the protein recognized by the receptor.

Edits on 20 Apr, 2018
Melanie Manipula
Melanie Manipula edited on 20 Apr, 2018
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Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins, such as surface proteins on cancer cells, that is added to immune cells for immunotherapy strategies such as directing T cells to fight cancer.

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Golden AI"Initial topic creation"
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 Chimeric antigen receptor

A lab engineered receptor designed to bind certain proteins, such as surface proteins on cancer cells, that is added to immune cells for immunotherapy strategies such as directing T cells to fight cancer.

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