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Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer

SIMPLE SUMMARY: Around thirty-five percent of pancreatic cancer patients present with locally advanced pancreatic cancer. These patients are treated with chemotherapy, and sometimes (stereotactic)radiotherapy can be added to the treatment regimen. In this study, we treated patients with locally adva...

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Autores principales: van ‘t Land, Freek R., Lau, Sai P., de Koning, Willem, Klaase, Larissa, Vink, Madelief, van Krimpen, Anneloes, Dumas, Jasper, Vadgama, Disha, Nuyttens, Joost J., Mustafa, Dana A. M., Stadhouders, Ralph, Willemsen, Marcella, Stubbs, Andrew P., Aerts, Joachim G., van Eijck, Casper H. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656492/
https://www.ncbi.nlm.nih.gov/pubmed/36358718
http://dx.doi.org/10.3390/cancers14215299
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author van ‘t Land, Freek R.
Lau, Sai P.
de Koning, Willem
Klaase, Larissa
Vink, Madelief
van Krimpen, Anneloes
Dumas, Jasper
Vadgama, Disha
Nuyttens, Joost J.
Mustafa, Dana A. M.
Stadhouders, Ralph
Willemsen, Marcella
Stubbs, Andrew P.
Aerts, Joachim G.
van Eijck, Casper H. J.
author_facet van ‘t Land, Freek R.
Lau, Sai P.
de Koning, Willem
Klaase, Larissa
Vink, Madelief
van Krimpen, Anneloes
Dumas, Jasper
Vadgama, Disha
Nuyttens, Joost J.
Mustafa, Dana A. M.
Stadhouders, Ralph
Willemsen, Marcella
Stubbs, Andrew P.
Aerts, Joachim G.
van Eijck, Casper H. J.
author_sort van ‘t Land, Freek R.
collection PubMed
description SIMPLE SUMMARY: Around thirty-five percent of pancreatic cancer patients present with locally advanced pancreatic cancer. These patients are treated with chemotherapy, and sometimes (stereotactic)radiotherapy can be added to the treatment regimen. In this study, we treated patients with locally advanced pancreatic cancer, after standard-of-care treatment with chemotherapy, with stereotactic body radiotherapy and an immunological adjuvant called IMM-101. We hypothesized that this combination treatment has the potential to induce a potent anti-tumor immune response. This study aimed to investigate the safety and immuno-modulatory effects of the treatment in the peripheral blood. The treatment demonstrated to be safe. Immune monitoring of the peripheral blood showed transient lymphodepletion and signs of immune activation after treatment. Moreover, immune activation after treatment correlated with improved progression-free survival. ABSTRACT: Background: Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients. Methods: LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood. Results: Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16−CD11b+HLA−DR(low) myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3. Conclusions: Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect.
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spelling pubmed-96564922022-11-15 Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer van ‘t Land, Freek R. Lau, Sai P. de Koning, Willem Klaase, Larissa Vink, Madelief van Krimpen, Anneloes Dumas, Jasper Vadgama, Disha Nuyttens, Joost J. Mustafa, Dana A. M. Stadhouders, Ralph Willemsen, Marcella Stubbs, Andrew P. Aerts, Joachim G. van Eijck, Casper H. J. Cancers (Basel) Article SIMPLE SUMMARY: Around thirty-five percent of pancreatic cancer patients present with locally advanced pancreatic cancer. These patients are treated with chemotherapy, and sometimes (stereotactic)radiotherapy can be added to the treatment regimen. In this study, we treated patients with locally advanced pancreatic cancer, after standard-of-care treatment with chemotherapy, with stereotactic body radiotherapy and an immunological adjuvant called IMM-101. We hypothesized that this combination treatment has the potential to induce a potent anti-tumor immune response. This study aimed to investigate the safety and immuno-modulatory effects of the treatment in the peripheral blood. The treatment demonstrated to be safe. Immune monitoring of the peripheral blood showed transient lymphodepletion and signs of immune activation after treatment. Moreover, immune activation after treatment correlated with improved progression-free survival. ABSTRACT: Background: Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients. Methods: LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood. Results: Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16−CD11b+HLA−DR(low) myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3. Conclusions: Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect. MDPI 2022-10-27 /pmc/articles/PMC9656492/ /pubmed/36358718 http://dx.doi.org/10.3390/cancers14215299 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van ‘t Land, Freek R.
Lau, Sai P.
de Koning, Willem
Klaase, Larissa
Vink, Madelief
van Krimpen, Anneloes
Dumas, Jasper
Vadgama, Disha
Nuyttens, Joost J.
Mustafa, Dana A. M.
Stadhouders, Ralph
Willemsen, Marcella
Stubbs, Andrew P.
Aerts, Joachim G.
van Eijck, Casper H. J.
Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer
title Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer
title_full Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer
title_fullStr Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer
title_full_unstemmed Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer
title_short Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer
title_sort immunomodulatory effects of stereotactic body radiotherapy and vaccination with heat-killed mycobacterium obuense (imm-101) in patients with locally advanced pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656492/
https://www.ncbi.nlm.nih.gov/pubmed/36358718
http://dx.doi.org/10.3390/cancers14215299
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