Advances in immunotherapy for pediatric acute myeloid leukemia

ABSTRACT

Introduction: Achieving better disease control in patients diagnosed with acute myeloid leukemia (AML) has proven challenging. Overall survival has been impacted by addressing treatment related mortality with focused supportive care measures. Despite this improvement, it remains difficult to induce durable leukemia remissions despite aggressive chemotherapeutic regimens. The addition of hematopoietic stem cell transplants (HSCT) has allowed further treatment intensification and provided the benefit of graft-versus-leukemia (GVL) effect. However, HSCT carries the risk of transplant related morbidities, particularly GVHD, and anti-tumor responsiveness is still suboptimal. Thus, there is a need for alternate therapies. Immunotherapy has the potential to address this need.

Areas covered: This review highlights promises and challenges to immune-based therapies for AML. It aims to summarize immunotherapeutic strategies trialed in AML patients to date, inclusive of: antibodies, vaccines, and cellular therapy. It emphasizes those being used in the pediatric population, but also includes adult clinical trials and translational science that may ultimately extend to pediatric patients.

Expert opinion: The elusiveness of an ideal surface antigen target together with an immunosuppressive leukemic microenvironment add to the already difficult challenge in developing AML-targeted immunotherapies. Though many hurdles remain, recent translational discovery and progressive clinical advances anticipate exciting future developments.

KEYWORDS:

• Acute myeloid leukemia
• immunotherapy
• antibodies
• vaccines
• T cell therapy
• NK cell therapy

Article highlights

• The outcome for AML remains poor, requiring new therapeutic approaches and immunotherapy has the potential to meet this challenge

• Immunotherapy using antibodies, vaccines, and cell therapy has shown promising results in preclinical studies

• The CD33-targted antibody drug conjugate gentuzumab ozogamycin is the most widely evaluated approach for AML in humans. Clinical studies have highlighted that careful patient selection is critical for efficacy and to prevent toxicity

• Clinical results of peptide and dendritic cell vaccines indicate that these approaches are safe, but require further optimization

• Adoptive transfer of conventional or genetically-modified T and NK cells are actively being explored in AML patients

• Checkpoint blockade holds the promise to reverse the immunosuppressive AML microenvironment

• There is a need for AML-specific immunotherapy target discovery, development of strategies to overcome the immunosuppressive AML microenvironment, and exploration of combinatorial therapies to improve immunotherapeutic efficacy for AML

This box summarizes key points contained in the article.

Declaration of interest

CL Bonifant, MP Velasquez and S Gottschalk have patent applications in the field of T Cell and gene-modified T-cell therapy for cancer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

The authors’ AML research is supported by grants from the Leukemia and Lymphoma Society, the Cancer Prevention Research Institute of Texas (RP160693), Alex Lemonade Stand Foundation, the Hyundai Hope on Wheels Foundation, the Damon Runyon Cancer Research Foundation, and the Ravitz Family Foundation.