Mannan-BAM, TLR ligands, and anti-CD40 immunotherapy in established murine pancreatic adenocarcinoma: understanding therapeutic potentials and limitations
| Autor: | Marketa Skalickova, Ondrej Uher, Andrea Frejlachova, Per Hansen, Karolina Kvardova, Veronika Caisova, Jan Zenka, Adéla Chlastáková, Karel Pacak, Jindrich Chmelar, Zhengping Zhuang, Jan Kopecky, Lucie Padoukova, Kamila Masakova, Radka Lencova, Anna Venhauerova |
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| Rok vydání: | 2021 |
| Předmět: |
Lipopolysaccharides
Cancer Research T-Lymphocytes medicine.medical_treatment Immunology Adenocarcinoma Ligands Article Mannans Pheochromocytoma Mice Cancer immunotherapy Antineoplastic Combined Chemotherapy Protocols Animals Immunology and Allergy Medicine CD40 Antigens Receptor biology business.industry Melanoma Toll-Like Receptors Imidazoles Immunotherapy medicine.disease Pancreatic Neoplasms Teichoic Acids Poly I-C Oncology Cancer research biology.protein Antibody business CD8 |
| Zdroj: | Cancer Immunol Immunother |
| ISSN: | 1432-0851 0340-7004 |
| DOI: | 10.1007/s00262-021-02920-9 |
| Popis: | Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths, and its therapy remains a challenge. Our proposed therapeutic approach is based on the intratumoral injections of mannan-BAM, toll-like receptor ligands, and anti-CD40 antibody (thus termed MBTA therapy), and has shown promising results in the elimination of subcutaneous murine melanoma, pheochromocytoma, colon carcinoma, and smaller pancreatic adenocarcinoma (Panc02). Here, we tested the short- and long-term effects of MBTA therapy in established subcutaneous Panc02 tumors two times larger than in previous study and bilateral Panc02 models as well as the roles of CD4(+) and CD8(+) T lymphocytes in this therapy. The MBTA therapy resulted in eradication of 67% of Panc02 tumors with the development of long-term memory as evidenced by the rejection of Panc02 cells after subcutaneous and intracranial transplantations. The initial Panc02 tumor elimination is not dependent on the presence of CD4(+) T lymphocytes, although these cells seem to be important in long-term survival and resistance against tumor retransplantation. The resistance was revealed to be antigen-specific due to its inability to reject B16-F10 melanoma cells. In the bilateral Panc02 model, MBTA therapy manifested a lower therapeutic response. Despite numerous combinations of MBTA therapy with other therapeutic approaches, our results show that only simultaneous application of MBTA therapy into both tumors has potential for the treatment of the bilateral Panc02 model. |
| Databáze: | OpenAIRE |
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