TNX-355 is a monoclonal antibody that binds to the CD4 receptor and inhibits virus entry. It is being developed by Tanox Biosystem and Biogen Inc.

TNX-355 is administered intravenously, and phase I dosing and safety studies in humans have been conducted. Current trials are being conducted in the United States.

One concern expressed about this kind of monoclonal antibody is the possibility that it could diminish immune system efficiency. If CD4 receptors are bound to monoclonal antibodies, then they may lose their facility to link to other immune cells in order to respond to antigens. However, studies conducted to date in animals and humans seem to demonstrate that this is not the case.

Current use

TNX-355 achieves adequate concentrations with weekly or fortnightly administration. A monotherapy dosing study conducted in 22 HIV-infected people compared three dosing regimens:

• 10mg/kg every seven days for ten weeks.

• 10mg/kg on the first day followed by 6mg/kg on day 7 and every 14 days thereafter for six doses.

• 25mg/kg every 14 days for five doses over 8 weeks.

After completing the treatment course, 23% of participants experienced a viral load reduction of greater than 1.4 log₁₀, whilst 64% experienced viral load reductions of greater than 1 log₁₀. In the majority of participants, virologic control appeared to wane as the study continued, suggesting that effective monotherapy with TNX-355 quickly results in drug resistance (Jacobson 2004).

TNX-355 is now being studied in treatment-experienced individuals receiving background therapy that has been optimised by resistance testing, in order to determine whether its virologic effect can be sustained.

Reference

Jacobson M et al. Phase 1b study of the anti-CD4 monoclonal antibody TNX-355 in HIV-infected subjects: safety and antiretroviral activity of multiple doses. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 536, 2004.