Back to Search
Start Over
Mannan-BAM, TLR ligands, and anti-CD40 immunotherapy in established murine pancreatic adenocarcinoma: understanding therapeutic potentials and limitations
- Source :
- Cancer Immunol Immunother
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14320851 and 03407004
- Volume :
- 70
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....98e14aad6fe09bd15c50111ed2cb3c55