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Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report

BACKGROUND: Desmoid tumors are intermediary malignant, fibrous lesions occurring in various soft tissues. Surgical treatment is relentlessly challenging because of the propensity for local aggressive behavior and high risk of recurrence. Consequently, a wide range of oncological drugs and radiation...

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Autores principales: Jebsen, Nina Louise, Apelseth, Torunn Oveland, Haugland, Hans Kristian, Rekdal, Øystein, Patel, Hamina, Gjertsen, Bjørn Tore, Jøssang, Dag Eirik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556957/
https://www.ncbi.nlm.nih.gov/pubmed/31177991
http://dx.doi.org/10.1186/s13256-019-2088-6
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author Jebsen, Nina Louise
Apelseth, Torunn Oveland
Haugland, Hans Kristian
Rekdal, Øystein
Patel, Hamina
Gjertsen, Bjørn Tore
Jøssang, Dag Eirik
author_facet Jebsen, Nina Louise
Apelseth, Torunn Oveland
Haugland, Hans Kristian
Rekdal, Øystein
Patel, Hamina
Gjertsen, Bjørn Tore
Jøssang, Dag Eirik
author_sort Jebsen, Nina Louise
collection PubMed
description BACKGROUND: Desmoid tumors are intermediary malignant, fibrous lesions occurring in various soft tissues. Surgical treatment is relentlessly challenging because of the propensity for local aggressive behavior and high risk of recurrence. Consequently, a wide range of oncological drugs and radiation therapy are being used; however, outcomes are unpredictable. We investigated whether local treatment with an oncolytic peptide could be beneficial in a patient with an unresectable desmoid tumor. CASE PRESENTATION: In a young 29-year-old Caucasian woman who was diagnosed with a retromammary desmoid tumor infiltrating deeply into the anterior thoracic wall, surgery was considered excessively mutilating, and observation was recommended. The lesion progressed, however, and caused debilitating pain, despite nonsteroidal anti-inflammatory medication. Subcutaneous injections of human interferon-α (Multiferon®) resulted in reduced growth kinetics but had to be terminated because of development of symptomatic pneumonitis. Frequently used oncological treatment was withheld because of the toxicity profile, and the patient was instead included in a phase I study investigating transdermal intratumoral injection of LTX-315, an oncolytic peptide that induces anticancer immune responses (ClinicalTrials.gov, NCT01986426). A marked increase of CD8(+) tumor-infiltrating T cells in the lesion was complemented by upregulation of immune gene signature (including effector T-cell, T-helper type 1 cell, chemokine, and cytokine genes). These changes were followed by gradual symptom relief and long-term disease stabilization, indicating clinical benefit. LTX-315 was well tolerated until termination in week 16 after a serious allergic reaction. CONCLUSIONS: Our patient was treated with repeated intratumoral injections of LTX-315, resulting in tumor regression accompanied by upregulation of immune genes and T-cell infiltration. Local application of immunotherapy, minimizing systemic side effects, represents a novel treatment modality in desmoid tumors that should be tested in further clinical trials.
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spelling pubmed-65569572019-06-13 Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report Jebsen, Nina Louise Apelseth, Torunn Oveland Haugland, Hans Kristian Rekdal, Øystein Patel, Hamina Gjertsen, Bjørn Tore Jøssang, Dag Eirik J Med Case Rep Case Report BACKGROUND: Desmoid tumors are intermediary malignant, fibrous lesions occurring in various soft tissues. Surgical treatment is relentlessly challenging because of the propensity for local aggressive behavior and high risk of recurrence. Consequently, a wide range of oncological drugs and radiation therapy are being used; however, outcomes are unpredictable. We investigated whether local treatment with an oncolytic peptide could be beneficial in a patient with an unresectable desmoid tumor. CASE PRESENTATION: In a young 29-year-old Caucasian woman who was diagnosed with a retromammary desmoid tumor infiltrating deeply into the anterior thoracic wall, surgery was considered excessively mutilating, and observation was recommended. The lesion progressed, however, and caused debilitating pain, despite nonsteroidal anti-inflammatory medication. Subcutaneous injections of human interferon-α (Multiferon®) resulted in reduced growth kinetics but had to be terminated because of development of symptomatic pneumonitis. Frequently used oncological treatment was withheld because of the toxicity profile, and the patient was instead included in a phase I study investigating transdermal intratumoral injection of LTX-315, an oncolytic peptide that induces anticancer immune responses (ClinicalTrials.gov, NCT01986426). A marked increase of CD8(+) tumor-infiltrating T cells in the lesion was complemented by upregulation of immune gene signature (including effector T-cell, T-helper type 1 cell, chemokine, and cytokine genes). These changes were followed by gradual symptom relief and long-term disease stabilization, indicating clinical benefit. LTX-315 was well tolerated until termination in week 16 after a serious allergic reaction. CONCLUSIONS: Our patient was treated with repeated intratumoral injections of LTX-315, resulting in tumor regression accompanied by upregulation of immune genes and T-cell infiltration. Local application of immunotherapy, minimizing systemic side effects, represents a novel treatment modality in desmoid tumors that should be tested in further clinical trials. BioMed Central 2019-06-10 /pmc/articles/PMC6556957/ /pubmed/31177991 http://dx.doi.org/10.1186/s13256-019-2088-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Jebsen, Nina Louise
Apelseth, Torunn Oveland
Haugland, Hans Kristian
Rekdal, Øystein
Patel, Hamina
Gjertsen, Bjørn Tore
Jøssang, Dag Eirik
Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report
title Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report
title_full Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report
title_fullStr Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report
title_full_unstemmed Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report
title_short Enhanced T-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide LTX-315: a case report
title_sort enhanced t-lymphocyte infiltration in a desmoid tumor of the thoracic wall in a young woman treated with intratumoral injections of the oncolytic peptide ltx-315: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556957/
https://www.ncbi.nlm.nih.gov/pubmed/31177991
http://dx.doi.org/10.1186/s13256-019-2088-6
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