Post-Transplant Vaccination with a Personalized Dendritic Cell/AML Fusion Cell Vaccine for Prevention of Relapse

Allogeneic transplantation is uniquely curative for a subset of patients with acute myeloid leukemia (AML) however, post-transplant relapse and graft versus host disease remain significant concerns. We have developed a vaccine in which patient-derived AML cells are fused with donor-derived dendritic cells (DCs), thereby presenting a broad array of antigens. Previous work (Rosenblatt Sci Transl Med) has suggested that such vaccines given in the first complete remission setting after chemotherapy consolidation elicit specific immune responses and can possibly lessen the risk of relapse. We hypothesize that donor-derived DC/AML vaccination post-transplant would elicit the durable expansion of leukemia- specific T cells within the donor T cell repertoire to effectively protect against disease relapse. We report the results of a phase 1 clinical trial (NCT03679650) evaluating the use of DC/AML fusion vaccine in patients with acute myeloid leukemia (AML) following allogeneic transplant. DC/AML fusion vaccine is generated with autologous leukemia blasts, cryopreserved at the time of diagnosis with AML, and donor-derived dendritic cells. DCs are collected via leukapheresis in pts in CR 25-70 days after an allogenic matched related or unrelated donor transplant (cohort A) or a haplo-identical donor (Cohort B). In order to proceed with leukapheresis, patients must demonstrate donor hematopoietic recovery and the absence of ongoing grade 2 or higher GVHD. For DC generation, donor-derived adherent mononuclear cells are cultured with GM-CSF, IL-4 and TNFa. Vaccine is administered subcutaneously starting day 70-100 post-transplant. 2 vaccines are given at 3 week intervals, in conjunction with 100 mcg GMCSF daily at the vaccine site for 4 days. A booster vaccine is given 30-60 days following the taper of immune suppression, in the absence of GVHD. Profiling of the immune microenvironment using single cell RNA sequencing from samples obtained before and after vaccination is being carried out. 17 participants have been enrolled. The median age was 59 years (range 23-74). 15 patients were enrolled to cohort A: 8 were transplanted with a matched unrelated donor and 7 were transplanted with a matched sibling donor. 2 participants were enrolled to cohort B. The median yield of leukemia cells was 207x10 6 (range 80-818x10 6)and mean viability was 96.5%. The median yield of DCs was 133x10 6 (range 29-182x10 6) and mean viability 72%. Fusion vaccine was successfully generated in