Table 1.
Human clinical trail therapy in cancer patients
| Tumor |
Treatment |
Clinical observations |
Mechanism |
References |
|---|---|---|---|---|
| CD40L gene therapy B-CLL (n = 11) |
CD40L-transfected leukemia cells, I.V. transfer |
No sever adverse reaction Flu-like symptoms Reduced leukemic cell count (>50% at 2–4 weeks postinfusion and lymph node size (>90% reduction) |
T-cell sensitization Agonist |
Wierda et al. (221) Kipps et al. (222) |
| CD40L-expressing leukemia cells with IL-2-expressing fibroblasts (n = 10) |
CD40L and IL-2 transduced leukemic blasts and skin fibroblasts, S.C. transfer |
No severe adverse reaction 90% 5-year survival rate |
Cytotoxic effector-cell activity Generation of IgG Ab Agonist |
Rousseau et al. (226) |
| Recombinant protein therapy Solid carcinomas and NHL (n = 32) |
Recombinant CD40L, S.C. injections, daily ×5 |
Some adverse reaction Injection site reaction Increased AST/ALT 38% Responders with stable disease 2 Partial responses |
Undetermined Agonist |
Vonderheide et al. (219) Younes et al. (220) |
| Anti-CD40 monoclonal antibody therapy Advanced solid tumors (n = 29) |
CP-870,893 (human IgG2, Pfizer, New York, NY, USA), I.V. infusion |
Some adverse reaction | Transient depletion of CD19+ B cells in blood |
Vonderheide et al. (219) |
| Cytokine release syndrome (chills, rigors, fever) 14% Partial responses of all patients and 27% in melanoma patients |
Agonist | |||
| NHL (n = 29) | SGN-40 (humanized IgG1, Seattle Genetics, Bothell, WA, USA), I.V. infusion |
Some adverse reactions Cytokine release syndrome 14% Partial response and 3.5% complete response |
Weak agonist | Forero-Torres et al. (218) |
| Multiple myeloma (n = 23) | Some adverse reaction Cytokine release syndrome 17% of patients had decreases in M-protein |
CD19+ B cell decrease Weak agonist |
Hussein et al. (225) | |
| CLL and multiple myeloma (n = 24) | HCD 122 (human IgG1, Novartis/XOMA, Basel, Switzerland) |
Some adverse reactions | Blocks CD40L-induced cell survival |
Byrd et al. (181) |
| Transient infusion reactions 8% Partial response |
Mediates ADCC Antagonist |
Bensinger et al. (179) |
B-CLL, B and chronic lymphocytic leukemias; I.V., intravenous; S.C., subcutaneous; AST, aspartate aminotransferase; ALT, alanine aminotransferase; NHL, non-Hodgkin’s lymphoma, Ig G, immunoglobulin G; IL-2, interleukin-2.