SYnAbs therapeutic anti-CD25 LO-TACT-1

Thanks to its unique platform, SYnAbs has been able to generate a new anti-IL-2R monoclonal antibody (LO-Tact-1), produced in the LOU/C rat species, available for clinical use in orthotopic transplant (OLT) program. This asset has been chimerized as IgG2bκ rat-LOU monoclonal antibody anti-IL2Ra and tested into several clinical studies as described below.

A prospective trial was conducted in 129 recipients of primary liver transplantation, to compare induction immunosuppression using triple drug therapy (cyclosporine, steroids, and azathioprine; group 1, n=42), versus triple drug therapy with a 10-day course of OKT3 (group 2, n=44) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 (group 3, n=43). Two-year actual patient survival rates were 64%, 79%, and 93% in groups 1, 2, and 3, respectively (1 vs. 2, NS; I vs. III, P=0.003; 2 vs. 3, NS). Up to 2 years after transplantation, 18%, 44%, and 53% of the grafts in groups 1, 2, and 3, respectively, had not experienced steroid-resistant acute rejection (1 vs. 2, P=0.002; 1 vs. 3, P=0.007; 2 vs. 3, NS). The overall incidence of chronic rejection was 4%. OKT3 therapy, but not LO-Tact-1, significantly increased the incidence of cytomegalovirus infections (P=0.019). In conclusion, immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3, without an increase in the incidence of infections.

Reding, Raymond; Feyaerts, Axel; Vraux, Hubert; Latinne, Dominique; De La Parra, Bernardo; Cornet, Anne; Cormont, Françoise; Jamart, Jacques; Sokal, Etienne; de Goyet, Jean de Ville; Lerut, Jan; Bazin, Hervé; Otte, Jean-Bernard. PROPHYLACTIC IMMUNOSUPPRESSION WITH ANTI-INTERLEUKIN-2 RECEPTOR MONOCLONAL ANTIBODY LO-TACT-1 VERSUS OKT3 IN LIVER ALLOGRAFTING: A Two-Year Follow-up Study. Transplantation: May 15, 1996 - Volume 61 - Issue 9 - p 1406-1409

To evaluate long-term patient and graft survival, and the incidence of acute and chronic rejection, infectious diseases and malignancies following induction therapy with a rat monoclonal interleukin 2 receptor antibody, Lo-Tact-1, or anti-thymocyte globulin (ATG). Forty first-time kidney transplant patients were prospectively randomized to two groups between May 1990 and June 1991. Twenty recipients were treated with Lo-Tact-1 (group 1) and the other 20, with ATG (group 2) during the first 14 days of the transplantation protocol. All patients were treated with azathioprine, steroids and cyclosporin A. Data were collected over 10 years. 

Beaudreuil S, Durrbach A, Noury J, Ducot B, Kriaa F, Bazin H, Charpentier B. Long-term results (10 years) of a prospective trial comparing Lo-tact-1 monoclonal antibody and anti-thymocyte globulin induction therapy in kidney transplantation. Transpl Int. 2006 Oct;19(10):814-20. doi: 10.1111/j.1432-2277.2006.00357.x. PMID: 16961773.