Co-stimulatory and Co-inhibitory Pathways in Autoimmunity.

Background. We wished to determine the safety and anti-human immunodeficiency virus (HIV) type 1 activity of single doses of TNX-355, a humanized IgG4 anti-CD4 monoclonal antibody with potent activity against HIV-1 in vitro, in HIV-infected subjects. Methods. Sequential cohorts of 6 HIV-1-infected subjects each received infusions of TNX-355. Data included plasma HIV-1 RNA level, CD4 + T cell count, TNX-355 coating of CD4 + T cells, and serum TNX-355 levels. Results. Dose-related reductions in plasma HIV-1 RNA loads correlated with complete CD4 + T cell coating by TNX-355. Peak median decreases in plasma HIV-1 RNA loads were 0.56, 1.33, and 1.11 log 10 copies/mL and occurred on days 4-7, 14, and 21 for the 3.0, 10, and 25 mg/kg doses, respectively. Dose-dependent increases in CD4 + T cell count occurred within 24 h of dosing. Conclusions. Single doses of TNX-355 reduced plasma HIV-1 RNA loads and increased CD4 + T cell counts in HIV-infected subjects. The further assessment of therapeutic potential awaits data from longer-duration trials.

Antiretroviral Activity of the Anti-CD4 Monoclonal Antibody TNX-355 in Patients Infected with HIV Type 1

Background Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4. Methods In this single-group,...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa1711460

Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1.

Molecular basis and therapeutic implications of CD40/CD40L immune checkpoint.

An antibody or a functional fragment thereof, acting agonistically or antagonistically on CD40.

Anti-CD40 monoclonal antibody

Preclinical assessment of anti-CD40 Mab 5D12 in cynomolgus monkeys

Development of anti-CD4 MAb hu5A8 for treatment of HIV-1 infection: preclinical assessment in non-human primates.

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Preclinical assessment of anti-CD40 Mab 5D12 in cynomolgus monkeys

Development of anti-CD4 MAb hu5A8 for treatment of HIV-1 infection: preclinical assessment in non-human primates.