Mismatched HLA class II presenting peptide antigens on recipient antigen-presenting and malignant hematopoietic cells (Mismatched HLA class II)

Mismatched HLA class II molecules, particularly HLA-DPB1, serve as critical therapeutic targets in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological malignancies. Unlike HLA class I, the constitutive expression of HLA class II is largely restricted to hematopoietic cells, including malignant leukemia and lymphoma cells, as well as professional antigen-presenting cells. This restricted expression pattern allows for the exploitation of donor-recipient HLA disparities to induce a potent and selective graft-versus-leukemia (GvL) effect. By targeting the specific complex of a mismatched HLA class II molecule and the peptide it presents, immunotherapies such as donor lymphocyte infusions (DLI) or engineered T-cell receptor (TCR) therapies can eradicate residual disease with a reduced risk of systemic graft-versus-host disease (GvHD). Clinical and preclinical programs, such as those utilizing bispecific T-cell engagers or CAR-T cells, focus on these mismatched antigens to provide 'off-the-shelf' or personalized cellular therapies for patients with high-risk blood cancers.

Other names

Mismatched HLA-DPB1Mismatched HLA-DRMismatched HLA-DQAllo-HLA class IIMismatched major histocompatibility complex class II

Targeting of mismatched HLA class II molecules (specifically HLA-DPB1) on the surface of recipient malignant hematopoietic cells and antigen-presenting cells by donor-derived or engineered T cells to induce a selective graft-versus-leukemia (GvL) effect while minimizing graft-versus-host disease (GvHD).