Korean J Hematol.  2011 Dec;46(4):229-238. 10.5045/kjh.2011.46.4.229.

Adenovirus as a new agent for multiple myeloma therapies: Opportunities and restrictions

• Raus S
• Coin S
• Monsurro V

• KMID: 2251983
• DOI: http://doi.org/10.5045/kjh.2011.46.4.229

Abstract

Multiple myeloma is a malignancy of B-cells that is characterized by the clonal expansion and accumulation of malignant plasma cells in the bone marrow. This disease remains incurable, and a median survival of 3-5 years has been reported with the use of current treatments. Viral-based therapies offer promising alternatives or possible integration with current therapeutic regimens. Among several gene therapy vectors and oncolytic agents, adenovirus has emerged as a promising agent, and it is already being used for the treatment of solid tumors in humans. The main concern with the clinical use of this vector has been its high immunogenicity; adenovirus is often able to induce a strong immune response in the host. Furthermore, new limitations in the efficacy of this therapy, intrinsic to the nature of tumor cells, have been recently observed. For example, our group showed a strong antiviral phenotype in vitro and in vivo in a subset of tumors, shedding new insights that may explain the partial failure of clinical trials based on this promising new therapy. In this review, we describe novel therapeutic approaches that implement viral-based treatments in hematological malignancies and address the novelty as well as the possible limitations of these new therapies, especially in the context of the use of adenoviral vectors for treating multiple myeloma.

Keyword

Adenovirus; Oncolytic therapy; Multiple myeloma; Antiviral phenotype

MeSH Terms

Adenoviridae
B-Lymphocytes
Bone Marrow
Genetic Therapy
Hematologic Neoplasms
Humans
Multiple Myeloma
Phenotype
Plasma Cells

Figure

• 

  Fig. 1 Different signaling pathways leading to the induction of virus stress-inducible genes (VSIGs) and interferon-stimulated genes (ISGs). Left: virus binding to TLR, stimulating the TLR/MyD88 pathway and leading to the activation and release of NF-κB into nucleus. Center: the dsRNA signaling pathway requires TLR3; there are at least 3 different mechanisms of inducing VSIGs. Right: the JAK/STAT pathway is activated by IFNα, -υ, -β, or -λ; the ISGF3 complex, consisting of STAT1, STAT2, and IRF9, is formed and translocates into nucleus, binding to the ISRE promoter sequence of different ISGs and components of the IFNγ pathway for the activation of GAS promoter sequences. IFNλ mediates the transcription of VSIGs and ISGs through initiation of ISREs or GASs. Abbreviations: TLR, Toll-like receptor; MyD88, myeloid differentiation primary response gene 88; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; IFN, interferon; ISGF, interferon stimulated gamma factor; IRF, interferon regulatory factor; ISRE, interferon stimulated response element; STAT, signal transducer and activator of transcription; GAS, interferon-activated site.

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