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Anti-PD-1 checkpoin...
Anti-PD-1 checkpoint blockade improves the efficacy of a melphalan-based therapy in experimental melanoma
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- Kiffin, Roberta (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Biomedicine, Department of Infectious Medicine,Sahlgrenska Center for Cancer Research (SCCR)
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- Johansson, Junko, 1989 (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Clinical Sciences, Department of Surgery
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- Olofsson Bagge, Roger, 1978 (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för kliniska vetenskaper, Avdelningen för kirurgi,Sahlgrenska Center for Cancer Research (SCCR),Institute of Clinical Sciences, Department of Surgery
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- Martner, Anna, 1979 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Sahlgrenska Centrum för Cancerforskning (SCCR),Institute of Biomedicine, Department of Infectious Medicine,Sahlgrenska Center for Cancer Research (SCCR)
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: Ejso. - : Elsevier BV. - 0748-7983. ; 47:9, s. 2460-2464
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Abstract
Subject headings
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- Introduction: The induction of adaptive cellular immunity in patients with in-transit melanoma metastasis treated with hyperthermic isolated limb perfusion (ILP) with melphalan has been shown to contribute to the effectiveness of the therapy. Activated CD8(+) T cells appear to be of particular importance for the efficacy of melphalan-based ILP therapy, as observed in both patients and animal models. In this study, we explored the possible synergistic effects of combining melphalan-based therapy with the checkpoint inhibitor anti-PD-1 on tumours in a mouse melanoma model. Methods: A murine vaccination model that utilized melphalan-exposed melanoma cells was used to mimic certain immunological features of melphalan-based ILP. The effects of the vaccine on tumour growth and PD-1 expression on CD8(+) tumour-infiltrating T cells were analyzed. The melphalan-based vaccine was then combined with an anti-PD-1 antibody and tumour growth was assessed. Results: Treatment with melphalan-based therapy significantly induced the expression of PD-1 on CD8(+) tumour-infiltrating lymphocytes. Combination therapy using melphalan-based therapy followed by treatment with PD-1 antibodies significantly reduced early-stage tumour growth relative to mono-therapies and no treatment. Conclusions: This study thus suggests that the addition of PD-1 blockade to melphalan-based therapies, such as ILP, may be therapeutically beneficial. (C) 2021 Published by Elsevier Ltd.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Cancer
- In-transit melanoma metastases
- Isolated limb perfusion (ILP)
- Immunotherapy
- Combination therapy
- isolated limb perfusion
- in-transit melanoma
- tumor-necrosis-factor
- infusion
- Oncology
- Surgery
Publication and Content Type
- ref (subject category)
- art (subject category)
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