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Abstract
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.
Highlights
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
Spontaneous regressions of melanoma[7] have been described and it is possible that the 5–10% of patients with metastatic disease that were cured from their disease prior to checkpoint inhibitors and targeted therapies[1] exhibited a better immune profile
Most melanoma tumors grow while being in the presence of tumor-infiltrating T-lymphocytes (TILs)
Summary
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. Immune checkpoint inhibitors and adoptive cell transfer (ACT) of autologous tumorinfiltrating 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. 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.
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