# Different immunotherapeutic combinations enhance specific T cell immune responses against leukemic cells, as well as leukemic progenitor cells, in acute myeloid leukemia

## TL;DR

Combining immunotherapies boosts T cell responses against leukemia and its stem cells, potentially improving treatment outcomes.

## Contribution

The study identifies effective immunotherapy combinations that target both leukemic cells and their progenitors.

## Key findings

- Anti-PD-1 antibodies combined with azacitidine strongly reduce leukemic progenitor growth.
- Leukemia-associated antigens stimulate T cell responses differently in patients with and without NPM1 mutations.
- Combination immunotherapies enhance antigen-specific immune responses against leukemia.

## Abstract

Immunotherapeutic approaches have become increasingly important in cancer therapy, including for patients with acute myeloid leukemia (AML). Despite being shown to be effective in the context of stem cell transplants for almost 50 years, further improvements are required to prevent relapse and its associated morbidity. The therapeutic use of immune checkpoint inhibition in AML is still under debate. We have shown some positive effects of it on cancer control ex vivo. We found that anti-programmed death-1 (PD-1) antibodies in combination with azacitidine (AZA) had the most pronounced effect on T-cell activation and control of leukemic progenitor/stem cell growth. We identified which leukemia-associated antigen (LAA) stimulated the largest IFNγ immune response by T cells from AML patients with and without the nucleophosmin 1 (NPM1) mutation and which immunotherapeutic strategy, either alone or in combination with the immune checkpoint anti-PD-1, could enhance immune responses against leukemic cells. Anti-PD-1 with AZA had a particularly strong effect with a mean colony reduction of 56%. Taken together, combinations of immunotherapeutic approaches increase antigen-specific immune responses against leukemic cells but also leukemic progenitor/stem cells. The combination of LAA-peptides with anti-PD-1 antibody and one further immunotherapeutic could be an interesting option for further clinical studies.