Vaccines as consolidation therapy for myeloid leukemia

Abstract

Immunotherapy for myeloid leukemias remains a cornerstone in the management of this highly aggressive group of malignancies. Allogeneic (allo) stem cell transplantation (SCT), which can be curative in acute and chronic myeloid leukemias, exemplifies the success of immunotherapy for cancer management. However, because of its nonspecific immune response against normal tissue, allo-SCT is associated with high rates of morbidity and mortality, secondary to graft-versus-host disease, which can occur in up to 50% of allo-SCT recipients. Targeted immunotherapy using leukemia vaccines has been heavily investigated, as these vaccines elicit specific immune responses against leukemia cells while sparing normal tissue. Peptide and cellular vaccines have been developed against tumor-specific and leukemia-associated self-antigens. Although not yet considered the standard of care, leukemia vaccines continue to show promising results in the management of the myeloid leukemias.

Conflict of interest statement

Financial & competing interests disclosure The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1. T-cell activation and killing of the target cell

In order for CD8+ T cells to be activated into antigen-specific cytotoxic T lymphocytes (CTLs), they must recognize the target antigen on APC and also receive signals from costimulatory molecules (e.g., CD80 and CD86). This causes CTL activation, which upon an encounter with the appropriate antigen on the target cell leads to target cell death. By contrast, antigen encounter without costimulation leads to T-cell anergy. APC: Antigen-presenting cell; MHC: Major histocompatibility complex; TCR: T-cell receptor.

Figure 2. Local skin reaction at the site of peptide vaccination

(A) Left thigh of a leukemia patient showing local painful erythema that developed at the injection site 2 weeks following vaccination with 1.0 mg PR1. (B) A small area of firm induration at a site of previous PR1 peptide vaccination on the anterior right thigh. This photograph was taken 1 year after vaccination with 0.5 mg PR1 peptide. (C) Skin biopsy from the local injection site shown in (A) demonstrating perivascular lymphocytic infiltrates (hematoxylin and eosin staining, 400×). A total of 39% of the lymphocytes were CD8+ T cells, 65% of which were specific for the PR1 peptide.