Identification of APOBEC3B as a potential target for the graft‐versus‐lymphoma effect by SEREX in a patient with mantle cell lymphoma

Abstract

SummaryRecently, a graft‐versus‐lymphoma (GVL) effect has been shown in patients allografted for mantle cell lymphoma (MCL), but the antigenic targets of this response remain unclear. We screened an MCL cDNA expression library with sera at GVL response after allogeneic haematopoietic stem cell transplantation and isolated five genes including APOBEC3B. Antibody responses to APOBEC3B were correlated with clinical response. Furthermore, APOBEC3B‐specific T‐cell response was induced with one of the HLA‐A*0201 binding peptides. In addition, APOBEC3B mRNA appeared to be upregulated in some MCL. These findings warrant further investigation of APOBEC3B as a candidate gene eliciting an effective immune response against MCL.

The allogeneic graft‐versus‐cancer effect

“…Moreover, development of antibody titres against RAFTK, but not against RBP‐Jkappa, was observed to be associated with disease regression following DLI treatment, suggesting that antibodies against CML‐associated antigens may contribute to the GVL effect. This hypothesis is further supported by other studies, which report association between the GVL effect and presence of antibodies against leukaemia‐specific proteins in CML (Yang et al , 2002), mantle cell lymphoma (Hishizawa et al , 2005), as well as adult T‐cell leukaemia (Hishizawa et al , 2006). In summary, there is data indicating a humoral contribution to the graft‐ versus ‐tumour (GVT) effects observed after allogeneic HSCT.…”

Autograft immune effector cells and survival in autologous peripheral blood hematopoietic stem cell transplantation

“…1 The indirect clinical evidence relies on the following observations: (1) anecdotal reports showing that withdrawal of immunosuppression in post-allogeneic stem cell transplantation tumor relapse resulted in clinical response; (2) less risk of relapse in patients receiving allogeneic grafts than in patients receiving syngeneic grafts; (3) the development of graft-versus-host disease triggers less relapse compared with no graft-versus-host disease in patients undergoing allogeneic stem cell transplantation; and (4) patients infused with a T-cell depleted allogeneic graft resulted in higher risk of relapse. 2 The direct clinical evidence of graft-versus-tumor effect in the allogeneic stem cell transplantation lies on the infusion of donor lymphocyte infusion (DLI) inducing remission after relapses occurred postallogeneic stem cell transplantation, 3 specifically the association of graft versus tumor effect and the presence of specific antibodies to tumor antigens, such as APOBEC3B in mantle cell lymphoma 4 and CML25 in chronic myelogenous leukemia and solid tumors. 5 In addition to the graft-versus-tumor effect, the infused allo-reactive immune effector cells can develop the detrimental complication of graft-versus-host disease leading to higher transplant-related mortality compared with APBHSCT.…”

A human monoclonal antibody drug and target discovery platform for B-cell chronic lymphocytic leukemia based on allogeneic hematopoietic stem cell transplantation and phage display

“…17 With the use of SEREX, serum antibodies from patients who received an alloHSC transplant followed by donor lymphocyte infusion (DLI) led to the identification of potential GVL antigens in chronic myelogenous leukemia [18][19][20][21] and multiple myeloma. 22,23 Even for patients who received an alloHSC transplant not followed by DLI, SEREX identified candidate GVL antigens in mantle cell lymphoma 24 and adult T-cell leukemia. 25 Alloreactive antibodies directed against H-Y antigens encoded on the Y chromosome, including minor histocompatibility antigen DBY, were discovered in male recipients with female donors.…”