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Clinical responses to adoptive T-cell transfer can be modeled in an autologous immune-humanized mouse model.

Journal article
Authors Henrik Jespersen
Mattias F Lindberg
Marco Donia
Elin Söderberg
Rikke Andersen
Ulrich Keller
Lars Ny
Inge Marie Svane
Lisa M Nilsson
Jonas A Nilsson
Published in Nature communications
Volume 8
Issue 1
ISSN 2041-1723
Publication year 2017
Published at Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Language en
Links dx.doi.org/10.1038/s41467-017-00786...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cancer and Oncology, Surgery

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.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.

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