Modified Dendritic cells as a therapeutic platform in hematologic malignancies with translational insights from central nervous system tumors.

Abstract

Dendritic cell (DC) vaccines elicit specific immune responses capable of precisely eliminating target cells. In recent years, numerous studies have explored the use of DC vaccination for treating hematological malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), as well as various non-leukemic cancers. DCs are utilized primarily through two strategies-in situ and ex vivo (canonical) approaches-to enhance anticancer immunity. The main DC subtypes employed in vaccines for AML and MDS are monocyte-derived DCs and leukemia-derived DCs. Various tumor-associated components have been used as antigen sources to load DCs, including peptides, recombinant proteins, apoptotic leukemic cells, whole tumor cells or lysates, and DCs/DCleu engineered to present a broader antigenic repertoire via RNA electroporation. Innovative strategies have been developed to improve DC vaccine efficacy, including combination therapies with conventional chemotherapy, monospecific or bispecific antibodies, and immune checkpoint inhibitors. Following a decade of challenges, the field has achieved meaningful progress and shows strong potential. This review summarizes recent advances in DC-based immunotherapy with a specific focus on hematologic malignancies, and incorporating comparative translational references from central nervous system tumors most notably glioblastoma to underscore both the common immunologic barriers and the unique mechanistic distinctions.