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Immuno-oncological effects of standard anticancer agents and commonly used concomitant drugs: an in vitro assessment.
Selvin, Tove; Berglund, Malin; Lenhammar, Lena; Lindskog, Magnus; Jarvius, Malin; Larsson, Rolf; Nygren, Peter; Fryknäs, Mårten; Andersson, Claes R.
Afiliación
  • Selvin T; Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, SE-75185, Uppsala, Sweden. tove.selvin@medsci.uu.se.
  • Berglund M; Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, SE-75185, Uppsala, Sweden.
  • Lenhammar L; Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, SE-75185, Uppsala, Sweden.
  • Lindskog M; Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185, Uppsala, Sweden.
  • Jarvius M; Department of Pelvic Cancer, Genitourinary Oncology Unit, Karolinska University Hospital, Stockholm, Sweden.
  • Larsson R; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
  • Nygren P; Department of Pharmaceutical Biosciences and Science for Life Laboratory, Uppsala University, SE-751 24, Uppsala, Box 591, Sweden.
  • Fryknäs M; Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, SE-75185, Uppsala, Sweden.
  • Andersson CR; Department of Immunology, Genetics and Pathology, Uppsala University, SE-75185, Uppsala, Sweden.
BMC Pharmacol Toxicol ; 25(1): 25, 2024 Mar 05.
Article en En | MEDLINE | ID: mdl-38444002
ABSTRACT

BACKGROUND:

It has become evident in the field of oncology that the outcome of medical treatment is influenced by the combined effect exerted on both cancer- and immune cells. Therefore, we evaluated potential immunological effects of 46 standard anticancer agents and 22 commonly administered concomitant non-cancer drugs.

METHODS:

We utilized a miniaturized in vitro model system comprised of fluorescently labeled human colon and lung cancer cell lines grown as monocultures and co-cultured with activated peripheral blood mononuclear cells (PBMCs). The Bliss Independence Model was then applied to detect antagonism and synergy between the drugs and activated immune cells.

RESULTS:

Among the standard anticancer agents, tyrosine kinase inhibitors (TKIs) stood out as the top inducers of both antagonism and synergy. Ruxolitinib and dasatinib emerged as the most notably antagonistic substances, exhibiting the lowest Bliss scores, whereas sorafenib was shown to synergize with activated PBMCs. Most concomitant drugs did not induce neither antagonism nor synergy. However, the statins mevastatin and simvastatin were uniquely shown to synergize with activated PBMC at all tested drug concentrations in the colon cancer model.

CONCLUSION:

We utilized a miniaturized tumor-immune model to enable time and cost-effective evaluation of a broad panel of drugs in an immuno-oncology setting in vitro. Using this approach, immunomodulatory effects exerted by TKIs and statins were identified.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Hidroximetilglutaril-CoA Reductasas / Neoplasias Pulmonares / Antineoplásicos Límite: Humans Idioma: En Revista: BMC Pharmacol Toxicol Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Hidroximetilglutaril-CoA Reductasas / Neoplasias Pulmonares / Antineoplásicos Límite: Humans Idioma: En Revista: BMC Pharmacol Toxicol Año: 2024 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido