Immunotherapy in multiple myeloma – possibility or probability?

Abstract

SummaryIn a small number of patients with multiple myeloma (MM), long-term disease-free survival has been achieved by harnessing the immune phenomenon, 'graft-versus-tumour' effect, induced by allogeneic haemopoietic stem cell transplantation. This has prompted many investigators to examine ways in which a patient's own immune system can be more effectively directed against their disease, with the ultimate aim of tumour eradication. In this review we assess the current understanding of immunobiology in MM, and how the different components of the immune system, such as dendritic cells, T cells and natural killer cells, may be harnessed using in-vitro and in-vivo priming techniques. We look at the clinical immunotherapy trials reported to date and whether, in light of the current information, immunotherapy for MM is an achievable goal.

Cellular immunotherapy in multiple myeloma: Lessons from preclinical models

“…In addition, it has been shown that long-term disease control can be achieved in a subset of MM patients after allo-SCT [71]. However, important challenges remain, as allo-SCT in MM is still associated with a relatively high relapse rate that could be explained by the immune suppressive phenotype of residual MM cells [8]. Moreover, the use of allo-SCT in MM also represents a certain risk of GvHD and transplantrelated mortality, despite the use of RIC regimens.…”

“…Both the number and the activity of several immune effector cells (Fig. 1) are affected by immune suppression in MM and this partially explains the anti-neoplastic activity of non-cellular immunotherapies, such as immunomodulatory drugs, which are able to revert immune effectors to their physiological functions [7][8][9][10][11][12].…”

“…Several of these T-cell alterations might occur due to the excessive production of TGF-β by MM cells, which suppresses T-cell responses through the inhibition of the IL-2 autocrine pathway in these cells [8,28]. In addition, Gorgun et al demonstrated that MM cells induce the expression of the suppressor of cytokine signaling (SOCS) 1 in CD4 and CD8 T cells, which is a negative regulator of IL-2, IFN-γ and IL-6 signaling, thus attenuating Th1 and CTL responses [12,24].…”

Genetically engineered attenuated measles virus specifically infects and kills primary multiple myeloma cells

“…As a proof of principle, recombinant MV that has been blinded for usage of CD46 and/or CD150 by site-specific mutagenesis within the H protein sequence has been rescued successfully, as have recombinants retargeted for usage of carcinoembryonic antigen or CD38 by fusion of the H protein open reading frame with that of the respective single-chain antibody (scFv) (Nakamura & Russell, 2004;Parato et al, 2005). For multiple myeloma (MM) cells in particular, several candidate surface antigens including MUC-1, sperm protein 17 and differentiation antigens such as CD38 and CD138 have been evaluated for targeted therapy, although with limited success to date (Greiner et al, 2000a;Treon et al, 2000;Harrison & Cook, 2005).…”

Cellular Immunotherapy Using Dendritic Cells Against Multiple Myeloma

“…Alternative approaches are clearly needed to prolong the disease-free survival as well as the overall survival of patients with MM. To prolong the survival of patients with MM who are undergoing allogeneic HSCT, donor lymphocyte infusion can be used successfully as a salvage therapy, which is based on the graft-versus myeloma effect in some cases of MM that relapse after allogeneic HSCT (Harrison & Cook, 2005;Perez-Simon et al, 2003). This role of immune effector cells provides the framework for the development of immune-based therapeutic options that use antigen-presenting cells (APCs) with increased potency, such as dendritic cells (DCs), in MM (Harrison & Cook, 2005).…”