CT-954: Intradermal Vididencel Vaccination in Measurable Residual Disease-Positive Acute Myeloid Leukemia Patients Results in Increased Antigen-Presenting Cells and T Cells at the Injection Site and Local Immune-Cell Interactions

Vididencel, an allogeneic leukemia-derived cell vaccine, is under development as a maintenance therapy for acute myeloid leukemia (AML) patients. The phase 2 ADVANCE-II study (NCT03697707) evaluated vididencel treatment in AML patients in CR1 with positive measurable residual disease (MRD + ) status. Intradermal vaccination with vididencel induced local skin reactions that correlated with systemic immune responses and clinical benefit (ASH2024, van de Loosdrecht). This study employed imaging mass cytometry in tissue sections for detailed single-cell analysis of dermal immune infiltrates at the injection site. AML patients in first complete remission with measurable residual disease (MRD + ) not slated for hematopoietic stem cell transplant received four biweekly vididencel doses followed by two booster doses at weeks 14 and 18. Skin biopsies were taken 2 days post the 1 st , 4 th , and 6 th vaccinations. Control samples included unvaccinated skin from two patients and healthy controls. Central lab analysis involved standard immunohistochemistry. For six patients at Haukeland University Hospital, imaging mass cytometry was performed on tissue sections stained with a 29-antibody panel. Regions of interest (1–4 mm 2 ) with immune infiltrates, identified via H&E staining, were scanned. Injection site reactions (redness, swelling, warmth), generally mild and short-lived, were reported in 88.5% of patients. Standard immunohistochemistry revealed substantial infiltration of CD4 + , CD8 + , and CD68 + cells compared with normal skin. Imaging mass cytometry corroborated these dense immune infiltrates. Further characterization of monocytes, dendritic cells, and T cells indicated close proximity, suggesting cell-to-cell interactions. For instance, granzyme B + /CD8 + T cells and CD38 + /CD4 + T cells were observed near CD1c + or CD141 + dendritic cells expressing high levels of HLADR, suggesting migration of patient dendritic cells from blood to skin and induction of a local immune response. Vididencel vaccination triggered a transient inflammatory skin reaction in most patients, indicative of a local immune response. Immunohistochemistry showed an influx of T cells and antigen-presenting cells, including dendritic cells. Multiparameter imaging mass cytometry further detailed the specific immune cell subsets infiltrating the injection sites. The observed co-localization of immune subsets post-vaccination supports the hypothesis of local antigen capture by blood-derived and resident antigen-presenting cells. This local immune response may ultimately contribute to a systemic anti-leukemic effect and disease control.