Use of a T cell-specific monoclonal antibody, T10B9, in a novel allogeneic stem cell transplantation protocol for hematologic malignancy high-risk patients

Abstract

To reduce the toxicity of traditional conditioning regimens for allogeneic stem cell transplantation (allo-SCT), we used single-agent chemotherapy conditioning with either busulfan (total cumulative dose, 16 mg/kg) or melphalan (200 to 240 mg/m 2 ), followed by the anti-T cell-specific monoclonal antibody T10B9 (MEDI-500) daily for 3 days. T cell-replete SCT was performed from HLA-identical sibling donors. Acute graft-versus-host disease (aGVHD) prophylaxis consisted of 7 additional days of T10B9 and delayed onset of cyclosporine (ie, on day +4 or +5). Twenty-six high-risk hematologic malignancy patients were entered onto this study. All 24 patients who survived longer than 8 days engrafted, although 1 patient experienced late graft failure. Deaths occurred in 21 of 26 patients because of infection (n = 7), progression/recurrence of primary disease (n = 6), aGVHD (n = 4), regimen-related toxicity (n = 1), and other causes (n = 3). Five of these patients are enjoying disease-free survival with a median survival of 1193 days after allo-SCT. The conditioning regimen induced modulation of surface expression of CD3 (but not CD4 or CD8) and was associated with decreasing tumor necrosis factor-alpha (but not interleukin-6) serum levels. In conclusion, single-agent chemotherapy conditioning with T10B9 produced durable engraftment and long-term survival in some patients who would not have qualified for a traditional allo-SCT.

Technical and Immunological Aspects of Face Transplantation

“…Elimination of mature T-cells is a critical mechanism of transplantation tolerance as was confirmed by many experimental and clinical studies (12)(13)(14)(15)(16)(17).…”

Ex vivo T-cell depletion in allogeneic hematopoietic stem cell transplant: past, present and future

“…63 The first lot of T10B9 was extracted from mouse ascites and approved by the US FDA (Food and Drug Administration) for T-cell depletion using complement-mediated lysis under BB-IND-4279. 64 , 65 , 66 T10B9 modulates the αβ but not the γδ TCR, in contrast to OKT3 which binds to the ε (epsilon) portion of the CD3 receptor and modulates the entire epitope, thus depleting CD3+ T cells (both αβ and γδ T cells). Immune reconstitution studies revealed that NK cell recovery was significantly greater in patients that received αβ TCD grafts than those who received unmanipulated grafts through the first year post transplant.…”

T10B9 monoclonal antibody: A short-acting nonstimulating monoclonal antibody that spares γδ T-cells and treats and prevents cellular rejection

“…(Figure 1). 1–11 Clearly there would be an advantage for a shorter acting immunosuppression agent which allows T-cell recovery, has little or no effect on B cells and, therefore, does not produce profound long-term immunosuppression.…”