Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model
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Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model. / Jespersen, Henrik; Lindberg, Mattias F; Donia, Marco; Söderberg, Elin M V; Andersen, Rikke; Keller, Ulrich; Ny, Lars; Svane, Inge Marie; Nilsson, Lisa M; Nilsson, Jonas A.
I: Nature Communications, Bind 8, 707, 2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model
AU - Jespersen, Henrik
AU - Lindberg, Mattias F
AU - Donia, Marco
AU - Söderberg, Elin M V
AU - Andersen, Rikke
AU - Keller, Ulrich
AU - Ny, Lars
AU - Svane, Inge Marie
AU - Nilsson, Lisa M
AU - Nilsson, Jonas A
PY - 2017
Y1 - 2017
N2 - Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 - a melanoma PDX model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2). Tumors that grow in PDXv2.0 are eradicated if the autologous tumor cells and T cells come from a patient that exhibited an objective response to ACT in the clinic. However, T cells from patients that are non-responders to ACT cannot kill tumor cells in PDXv2.0. Taken together, PDXv2.0 provides the potential framework to further model genetically diverse human cancers for assessing the efficacy of immunotherapies as well as combination therapies.Combining different types of immune therapies might benefit certain patients. Here, the authors develop an autologous immune-humanized melanoma mouse model that allows the preclinical assessment of cancer cell-T cell interactions from each individual patient and the benefits of immunotherapies combinations.
AB - Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumor-infiltrating T cells have shown durable responses in patients with melanoma. To study ACT and immunotherapies in a humanized model, we have developed PDXv2.0 - a melanoma PDX model where tumor cells and tumor-infiltrating T cells from the same patient are transplanted sequentially in non-obese diabetic/severe combined immune-deficient/common gamma chain (NOG/NSG) knockout mouse. Key to T-cell survival/effect in this model is the continuous presence of interleukin-2 (IL-2). Tumors that grow in PDXv2.0 are eradicated if the autologous tumor cells and T cells come from a patient that exhibited an objective response to ACT in the clinic. However, T cells from patients that are non-responders to ACT cannot kill tumor cells in PDXv2.0. Taken together, PDXv2.0 provides the potential framework to further model genetically diverse human cancers for assessing the efficacy of immunotherapies as well as combination therapies.Combining different types of immune therapies might benefit certain patients. Here, the authors develop an autologous immune-humanized melanoma mouse model that allows the preclinical assessment of cancer cell-T cell interactions from each individual patient and the benefits of immunotherapies combinations.
KW - Animals
KW - Antibodies, Monoclonal, Humanized/therapeutic use
KW - Antineoplastic Agents/therapeutic use
KW - Cell Line, Tumor
KW - Humans
KW - Immunotherapy, Adoptive
KW - Interleukin Receptor Common gamma Subunit/genetics
KW - Interleukin-2/genetics
KW - Lymphocytes, Tumor-Infiltrating/immunology
KW - Melanoma/immunology
KW - Mice, Knockout
KW - Neoplasm Metastasis
KW - Skin Neoplasms/immunology
KW - T-Lymphocytes/immunology
U2 - 10.1038/s41467-017-00786-z
DO - 10.1038/s41467-017-00786-z
M3 - Journal article
C2 - 28955032
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 707
ER -
ID: 196038244