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Coley's immunotherapy revived: Innate immunity as a link in priming cancer cells for an attack by adaptive immunity
O. Uher, V. Caisova, P. Hansen, J. Kopecky, J. Chmelar, Z. Zhuang, J. Zenka, K. Pacak,
Language English Country United States
Document type Journal Article, Research Support, N.I.H., Intramural, Review
Grant support
ZIA HD008735-18
Intramural NIH HHS - United States
- MeSH
- Adaptive Immunity MeSH
- Phagocytosis drug effects immunology MeSH
- Immune System immunology metabolism MeSH
- Immunomodulation MeSH
- Immunotherapy * methods MeSH
- Combined Modality Therapy MeSH
- Humans MeSH
- Ligands MeSH
- Tumor Microenvironment drug effects genetics immunology MeSH
- Neoplasms etiology metabolism pathology therapy MeSH
- Immunity, Innate MeSH
- Antineoplastic Agents, Immunological pharmacology therapeutic use MeSH
- Toll-Like Receptors metabolism MeSH
- Treatment Outcome MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Research Support, N.I.H., Intramural MeSH
There is no doubt that immunotherapy lies in the spotlight of current cancer research and clinical trials. However, there are still limitations in the treatment response in certain types of tumors largely due to the presence of the complex network of immunomodulatory and immunosuppressive pathways. These limitations are not likely to be overcome by current immunotherapeutic options, which often target isolated steps in immune pathways preferentially involved in adaptive immunity. Recently, we have developed an innovative anti-cancer immunotherapeutic strategy that initially elicits a strong innate immune response with subsequent activation of adaptive immunity in mouse models. Robust primary innate immune response against tumor cells is induced by toll-like receptor ligands and anti-CD40 agonistic antibodies combined with the phagocytosis-stimulating ligand mannan, anchored to a tumor cell membrane by biocompatible anchor for membrane. This immunotherapeutic approach results in a dramatic therapeutic response in large established murine subcutaneous tumors including melanoma, sarcoma, pancreatic adenocarcinoma, and pheochromocytoma. Additionally, eradication of metastases and/or long-lasting resistance to subsequent re-challenge with tumor cells was also accomplished. Current and future advantages of this immunotherapeutic approach and its possible combinations with other available therapies are discussed in this review.
References provided by Crossref.org
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