General AML

Novel immunotherapeutic approaches in AML: Vaccines

Despite the great advancements in treatment for Acute Myeloid Leukemia (AML), high relapse rates are still a concern. Immunotherapy may provide an alternative approach to chemotherapy. In fact, the American Society of Clinical Oncology (ASCO) named immunotherapy in cancer as the ‘Advance of the Year’ in its Clinical Cancer Advances 2016 report.

According to Soumaya Karaki et al., cancer vaccines trigger an anti-tumor immune response after immunization with a defined tumor-specific antigen or modified tumor cells. The use of vaccines in AML is still under development. Kazusa Ishii and Austin J. Barrett conducted a review of vaccine therapy in AML. This review was published in Therapeutic Advances in Hematology. They state that there are a few studies in this area of development and the clinical benefits have been unclear. For example, in a phase I/II study single epitopes of WT1 and PR1 peptides were given with adjuvant to patients with AML and/or Myelodysplastic Syndrome (MDS) there were huge reductions in Minimal Residual Disease (MRD) through the increase in PR1 and WT1 specific T-cells, although Kazusa Ishii and Austin J. Barrett report that these effects did not correlate to a meaningful clinical response.

Yet, trials using the WT1 peptide alone in 51 patients with MDS and/or AML reviewed by Di Stasi et al., and part of the report by Kazusa Ishii and Austin J. Barrett, demonstrated more promising effects of this vaccine. In terms of tolerability, there were not any safety concerns and, in terms of clinical response, some patients achieved disease-free survival of up to 8 years.

Kazusa Ishii and Austin J. Barrett also reviewed the use of vaccines after Hematopoietic Stem-Cell Transplant (HSCT). They report that this approach has the following benefits:

  • A lower tumor burden early after HSCT phase provides an ideal setting for anti-tumor immune responses to take place
  • At the time of transplantation, the unique immune setting around, characterized by regulatory T-cell depletion, lymphopenia and the release of interleukins (such as IL-7, IL-15 and IL-21), facilitates the triggering of anti-leukemia immune responses
  • HSCT offers the chance to link vaccination with administration of leukemia specific cells, either vaccinating patients post-cell infusion or via donor vaccination

In summary the use of vaccine therapy has potential, nonetheless, authors state there is a need to further investigate this therapy through large randomized clinical trials.

 

Abstract

There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus-leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures.

References
  1. American Society of Clinical Oncology. A Message From ASCO’s President: Clinical Cancer Advances 2016. http://www.asco.org/research-progress/reports-studies/clinical-cancer-advances#/message-ascos-president-0. [Accessed November 2016].
  2. Karaki S. et al. Is There Still Room for Cancer Vaccines at the Era of Checkpoint Inhibitors? Vaccines (Basel). 2016 Nov 3; 4(4):37. DOI:10.3390/vaccines4040037.
  3. Ishii K. & Barrett A.J. Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic). Ther Adv Hematol. 2016 Feb; 7(1):17–39. DOI: 10.1177/2040620715616544.