Leukemic cells expressing inherited paternal HLA antigens and non-inherited maternal HLA antigens (IPA/NIMA-targeted leukemic cells)

This target refers to the specific antigenic profile of leukemic cells in the context of allogeneic hematopoietic stem cell transplantation (HSCT), particularly haploidentical or cord blood transplants. The target is defined by the presence of Inherited Paternal HLA Antigens (IPA) and the absence of Non-Inherited Maternal HLA Antigens (NIMA) on the patient's cells, or vice versa, depending on the donor-recipient relationship. In maternal-to-child transplants, the mother's T cells are naturally primed against the child's IPA (antigens inherited from the father), leading to a potent Graft-versus-Leukemia (GvL) effect (Scaradavou et al., 2009). Conversely, Non-Inherited Maternal Antigens (NIMA) are used to select donors that minimize Graft-versus-Host Disease (GvHD), as the recipient's immune system may have developed a degree of tolerance to these antigens in utero (van Rood et al., 2002). This approach aims to optimize the balance between anti-tumor efficacy and transplant-related toxicity in patients with high-risk hematologic malignancies (Ichinohe et al., 2004). Clinical trials have explored the safety and efficacy of adoptive immunotherapy using NIMA-compatible and IPA-targeted cord blood units (NCT01295931).

Other names

NIMA-mismatched leukemic cellsIPA-targeted leukemic cellsHaploidentical transplant targetsMaternally-primed leukemic targets

Donor T-cell mediated cytotoxicity against mismatched HLA antigens (IPA) and exploitation of immunological tolerance to non-inherited maternal antigens (NIMA).