Progress of dendritic cell-based cancer vaccines for patients with hematological malignancies

ABSTRACT

Introduction: Dendritic cells (DCs) are the most professional antigen-presenting cells eliciting cellular and humoral immune responses against cancer cells by expressing these antigens on MHC class I/II complexes to T cells. Therefore, they have been employed in many clinical trials as cancer vaccines for patients with cancer. This review focuses on the use of DCs in leukemia patients expressing leukemia-associated antigens (LAAs).

Areas covered: The contribution of both stimulating vs. tolerogenic DCs as well as of other factors to the milieu of anti-leukemia immune responses are discussed. Several DC vaccination strategies like leukemia lysate, proteins and peptides have been developed. Next generation DC vaccines comprise transduction of DCs with retroviral vectors encoding for LAAs, cytokines and costimulatory molecules as well as transfection of DCs with naked RNA encoding for LAAs. Published as well as ongoing clinical trials are reported and critically reviewed.

Expert opinion: Future results will demonstrate whether next-generation DCs are really superior to conventional pulsing with peptide, protein or tumor lysate. However, currently available methods based on nucleic acid transfection/transduction are tempting in terms of material production costs and time for clinical application according to good manufacturing practice (GMP).

KEYWORDS:

• Dendritic cells (DCs)
• cancer vaccines
• leukemia
• cancer antigens
• gene transfer

Article highlights

• DCs link the innate and adaptive immune system and prime tumor specific T cells by presenting tumor associated antigens (TAA).

• Function of DCs is downregulated by tumor induced immunosuppressive environment.

• DC vaccines are generated using whole tumor cells, leukemia derived DCs, tumor cell lysates or by the administration of peptides.

• Many ongoing and published clinical trials show promising results and have been summarized in this review.

• Next generation DC vaccines are based on nucleic acid encoding antigens: either transfected with electroporation or transduced with viral vectors.

• Next generation DC vaccines cover all HLA types and allow DCs to overcome the immunosuppressive tumor milieu through genetic engineering.

This box summarizes key points contained in the article.

Declaration of interest

Ming Ni received financial support from the China Scholarship Council. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.