New insights into antigen specific immunotherapy for chronic myeloid leukemia

Yangqiu Li,Chen Lin,Christian A Schmidt

doi:10.1186/1475-2867-12-52

Yangqiu Li, Chen Lin + Show 1 more

Open Access

https://doi.org/10.1186/1475-2867-12-52

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Abstract

Chronic myeloid leukemia (CML) is a stem cell disease in which BCR/ABL plays an important role as an oncoprotein and a molecular and immunogenic target. Despite the success of targeted therapy using tyrosine kinase inhibitors (TKIs), CML remains largely incurable, most likely due to the treatment resistance of leukemic stem cells. Several immunotherapies have been developed for CML in different stages and relapse after allogeneic stem cell transplantation. In the this review, several specific immunotherapeutic approaches for CML, including vaccination and adoptive cellular immunotherapy, are discussed along with results from clinical trials, and the value of such immunotherapies in the era of imatinib and leukemia-associated antigens (LAAs), which are capable of inducing specific T cell responses and are appropriate target structures for the immunological targeting of CML cells, are also summarized.

Highlights

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder that is characterized by a t(9;22) translocation, which results in the expression of BCR-ABL fusion oncoproteins that are unique to the leukemic cells, necessary for oncogenesis, and potentially immunogenic [1]
The decrease in BCR-ABL mRNA levels was associated with an increase in the frequency of Wilms' tumor 1 (WT1)-specific CTLs [33]. These findings indicated that WT1 peptide vaccines may become a safe and cure-oriented treatment for patients with CML who have residual disease despite imatinib treatment
Conclusions and future investigation Data from vaccination and adoptive T cell immunotherapy for CML have indicated that the immune system may contribute to disease control in CML

Summary

Introduction

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder that is characterized by a t(9;22) translocation, which results in the expression of BCR-ABL fusion oncoproteins that are unique to the leukemic cells, necessary for oncogenesis, and potentially immunogenic [1]. In an additional phase-I/II study, autologous DCs were generated from peripheral blood monocytes and used as a vaccine in patients with chronic phase CML who had not achieved an adequate cytogenetic response after IFN-α or imatinib treatment and demonstrated that T cells that recognize leukemia-associated antigens become detectable [49]. The antigenprocessing defects may be a consequence of the reduced capacity of CML-DCs to capture antigens via macropinocytosis or mannose receptors when compared with DCs generated from healthy individuals This is due to the PKC-induced differentiation associated with the down-regulation of BCR-ABL activity, which raises the possibility that CML-derived DC vaccines will be less effective in presenting leukemia-specific Ags [44]. Cytotoxicity against a tumor cell line endogenously expressing the p210 (BCR-ABL) b3a2 variant fusion region was demonstrated This developed construct may serve as a candidate vaccine for gene-based, antigen-specific CML immunotherapy [51]. The novel hchTCR specific for CML cells can be expressed, normally presented on the cell surface, and may be used to redirect human T cells [72]

Conclusions and future investigation

21. Vonka V

Findings

56. Huang XJ