Local administration of a novel Toll-like receptor 7 agonist in combination with doxorubicin induces durable tumouricidal effects in a murine model of T cell lymphoma.

Abstract

BACKGROUND:

Conventional chemotherapy and radiotherapy for the treatment of lymphoma have notable drawbacks, and passive immunotherapy using a monoclonal antibody is restricted to CD20-positive B cell lymphoma. Therefore, new treatment types are urgently required, especially for T cell lymphoma. One type of new antitumour therapy is the use of active immunotherapeutic agents, such as agonists of the Toll-like receptors (TLRs), which facilitate the induction of prolonged antitumour immune responses.

METHODS:

We have synthesised a novel TLR7 agonist called SZU-101 and investigated the systemic antitumour effect on a murine model of T cell lymphoma in vivo.

RESULTS:

Here, we report that the intratumoural administration of SZU-101 enhanced the effectiveness of a conventionally used chemotherapeutic agent, doxorubicin (DOX). SZU-101 administration improved tumour clearance in a murine model of T cell lymphoma. The novel combination of intratumourally administered SZU-101 and DOX generated strong cytokine production and enhanced the cytotoxic T lymphocyte response, leading to the eradication of both local and distant tumours in tumour-bearing mice.

CONCLUSIONS:

These findings suggested that combined active immunotherapy can be developed as a promising treatment for T cell lymphoma, which may further improve the effectiveness of the current standard cyclophosphamide, DOX, vincristine and prednisone (CHOP) therapy.

• Authors: Jiang Zhu, Shiping He, Jie Du, Zhulin Wang, Wang Li, Xianxiong Chen, Wenqi Jiang, Duo Zheng, Guangyi Jin
• Journal: Journal of hematology & oncology (J Hematol Oncol) Vol. 8 Pg. 21 (Mar 04 2015) ISSN: 1756-8722 [Electronic] England
• PMID: 25887995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Membrane Glycoproteins
• SZU-101
• Succinates
• Tlr7 protein, mouse
• Toll-Like Receptor 7
• Doxorubicin
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Blotting, Western
• Disease Models, Animal
• Doxorubicin (administration & dosage)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Lymphoma, T-Cell (pathology)
• Membrane Glycoproteins (agonists)
• Mice
• Mice, Inbred C57BL
• Succinates (pharmacology)
• Toll-Like Receptor 7 (agonists)