TLR9 agonist MGN1703 enhances B cell differentiation and function in lymph nodes

Area of Science:

• Immunology
• Oncology
• Virology

Background:

• Toll-like receptor 9 (TLR9) agonists are investigated for immunotherapy against cancer and infections.
• TLR9 is mainly found in B cells and plasmacytoid dendritic cells (pDCs), crucial for immune responses.
• The in vivo effects of TLR9 agonism on human lymph node B cells remain largely unknown.

Purpose of the Study:

• To investigate the in vivo effects of the TLR9 agonist MGN1703 on human lymph node immune cells.
• To assess MGN1703's impact on B cell activity and immune responses within lymph nodes as part of an HIV cure strategy trial.

Main Methods:

• Seven participants received MGN1703 (lefitolimod) for 24 weeks alongside antiretroviral therapy.
• Lymph node biopsies were collected at baseline and after 24 weeks for immunologic and virologic analysis.

Main Results:

• MGN1703 treatment led to increased B cell differentiation, activated pDCs, NK cells, and T cells.
• A significant interferon response was observed, alongside elevated Activation-Induced cytidine Deaminase expression, crucial for B cell diversification.
• Increased IgG production and altered antibody glycosylation patterns were noted during MGN1703 treatment.

Conclusions:

• The TLR9 agonist MGN1703 effectively modulates human lymph node B cells in vivo.
• These findings support further development of TLR9 agonists for immunotherapy in cancer and infectious diseases.