Journal
CANCERS
Volume 14, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/cancers14122994
Keywords
acute myeloid leukemia; vaccination; immunotherapy; dendritic cells
Categories
Funding
- Italian Ministry of Health-Current research IRCCS
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Immunotherapy is revolutionizing the treatment of hematologic diseases. However, in acute myeloid leukemia (AML), the options have been limited to one approved drug, gemtuzumab ozogamicin. This review focuses on the use of vaccines in AML and discusses their biological mechanisms and clinical impact. Various vaccine strategies have been explored, with promising results in terms of toxicity and application in elderly patients. However, the clinical outcomes are still unsatisfactory, and further research is needed to determine the best approach. Vaccines have advantages of being less toxic and more manageable compared to other immunotherapeutic strategies. However, their effectiveness may be limited in active or high-burden disease. Future studies should aim to optimize immunotherapy-based strategies, including the use of vaccines, to achieve long-term disease control in AML.
Simple Summary Immunotherapy is changing the therapeutic landscape of many hematologic diseases. Nevertheless, in acute myeloid leukemia (AML) the anti CD33 antibody-drug conjugate gemtuzumab ozogamicin is the only approved drug. In this review, we aimed at reporting biological mechanisms and their clinical impact of vaccines in AML. The principal vaccination strategies have been analyzed and commented, highlighting advantages in terms of toxicity and possibility to apply in elderly patients. Nevertheless, the clinical results of this strategy in AML are still far from satisfactory. It is necessary to evaluate the best scenario for this approach, whether in a therapeutic, prophylactic, or preemptive setting, considering the poorer results in active or high-burden disease. Finally, we underlined the necessity in AML of further research to optimize immunotherapy-based strategies, among which vaccines might represent relevant actors to contribute to long-term disease control. Immunotherapy is changing the therapeutic landscape of many hematologic diseases, with immune checkpoint inhibitors, bispecific antibodies, and CAR-T therapies being its greatest expression. Unfortunately, immunotherapy in acute myeloid leukemia (AML) has given less brilliant results up to now, and the only approved drug is the antiCD33 antibody-drug conjugate gemtuzumab ozogamicin. A promising field of research in AML therapy relies on anti-leukemic vaccination to induce remission or prevent disease relapse. In this review, we analyze recent evidence on AML vaccines and their biological mechanisms. The principal proteins that have been exploited for vaccination strategies and have reached clinical experimental phases are Wilm's tumor 1, proteinase 3, and RHAMM. the majority of data deals with WT1-base vaccines, given also the high expression and mutation rates of WT1 in AML cells. Stimulators of immune responses such as TLR7 agonist and interleukin-2 have also proven anti-leukemic activity both in vivo and in vitro. Lastly, cellular vaccines mainly based on autologous or allogeneic off-the-shelf dendritic cell-based vaccines showed positive results in terms of T-cell response and safety, also in elderly patients. Compared to other immunotherapeutic strategies, anti-AML vaccines have the advantage of being a less toxic and a more manageable approach, applicable also to elderly patients with poorer performance status, and may be used in combination with currently available therapies. As for the best scenario in which to use vaccination, whether in a therapeutic, prophylactic, or preemptive setting, further studies are needed, but available evidence points to poorer results in the presence of active or high-burden disease. Given the poor prognosis of relapsed/refractory or high-risk AML, further research is urgently needed to better understand the biological pathways that sustain its pathogenesis. In this setting, research on novel frontiers of immunotherapy-based agents, among which vaccines represent important actors, is warranted to develop new and efficacious strategies to obtain long-term disease control by immune patrolling.
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