Anti-PD-1 checkpoint blockade improves the efficacy of a melphalan-based therapy in experimental melanoma

Kiffin, RobertaGothenburg 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) (författare)

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.

Johansson, Junko,1989Gothenburg 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(Swepub:gu)xjojun (författare)
Olofsson Bagge, Roger,1978Gothenburg 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(Swepub:gu)xoloro (författare)
Martner, Anna,1979Gothenburg 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)(Swepub:gu)xbigan (författare)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för infektionssjukdomar (creator_code:org_t)

Av författaren/redakt...: Kiffin, Roberta; Johansson, Junko ...; Olofsson Bagge, ...; Martner, Anna, 1 ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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