CIK Cells and HDAC Inhibitors in Multiple Myeloma

Abstract

Multiple myeloma is the second most common hematological malignancy. Despite all the progress made in treating multiple myeloma, it still remains an incurable disease. Patients are left with a median survival of 4–5 years. The combined treatment of multiple myeloma with histone deacetylase inhibitors and cytokine-induced killer cells provides a promising targeted treatment option for patients. This study investigated the impact of a combined treatment compared to treatment with histone deacetylase inhibitors. The experiments revealed that a treatment with histone deacetylase (HDAC) inhibitors could reduce cell viability to 59% for KMS 18 cell line and 46% for the U-266 cell line. The combined treatment led to a decrease of cell viability to 33% for KMS 18 and 27% for the U-266 cell line, thus showing a significantly better efficacy than the single treatment.

MMP9-Associated Tumor Stem Cells, CCL1-Silenced Dendritic Cells, and Cytokine-Induced Killer Cells Have a Remarkable Therapeutic Efficacy for Acute Myeloid Leukemia by Activating T Cells

“…DC has a significant effect in both innate and acquired immunity, which is particularly important for the treatment of tumors with low endogenous immune response, such as AML [ 40 , 41 ]. Previous studies have verified that CIK cells can significantly kill a variety of tumor cells such as leukemia [ 42 ], multiple myeloma [ 43 ], and lymphoma [ 44 , 45 ]. Researches have disclosed that the coculture of CIK cells with DC can improve the antitumor activity of CIK cells [ 46 , 47 ].…”

30 years of CIK cell therapy: recapitulating the key breakthroughs and future perspective

“…To expand the horizon beyond the pivotal role of NKG2D in CIK cell-mediated cytotoxicity, the additional axis of ADCC (via CD16 or other yet to be known factors) requires further attention. On broader prospective, besides the first line classical treatment (chemotherapy, Sharma and Schmidt-Wolf J Exp Clin Cancer Res (2021) 40:388 radiotherapy), CIK therapy continues to evolve in parallel with other immunotherapies by synergising with advanced immunologic approaches like antibody therapy (monoclonal antibody, bispecific monoclonal antibodies, bispecific T-cell engager (BiTE) antibody), checkpoint/epigenetic inhibitors, chimeric antigen receptor T cell CAR-T cell therapy, allogeneic hematopoietic cell transplantation (alloHCT), Antibody-drug conjugates (ADCs), combination with cytokine inhibitors and recently proposed CIK/DC-CIK cells with nanomaterials [7][8][9]. Although mild graft-versus-host disease (GVHD) is still a concern in a subset of patients treated with CIK cells, experience from previous clinical trials suggests that these are largely manageable [10].…”

Synergistic integration of histone deacetylase inhibitors apparently enhances the cytokine‐induced killer cell efficiency in multiple myeloma via the NKG2D pathway

“…sodium butyrate, valproic acid and trichostatin A) in combination with CIK cells (as the first preclinical model) and confirmed their significant impact on human MM cell lines (KMS-18 and U-266). 14 However, some questions remain unanswered, such as (1) what exactly are the mechanisms behind the synergistic effect of CIK cells with HDACis in MM and (2) whether genetic/gender differences could play a therapeutically restrictive role when testing HDACis-CIK combinations in clinics, because MM is known to occur more frequently in males compared with females. Considering this, herein, we extended our analysis by testing clinically applicable HDACis with CIK cells in genetically distinct MM cell lines.…”