Therapeutic application of thalidomide in multiple myeloma

2001 ◽  
Vol 28 (6) ◽  
pp. 583-587 ◽  
Author(s):  
Robert A. Kyle ◽  
S. Vincent Rajkumar
Keyword(s):  
Multiple Myeloma ◽  
Therapeutic Application

Indirubin-3’-Monoxime Acts as a Novel Proteasome Inhibitor: Therapeutic Application in Multiple Myeloma

2021 ◽  
Author(s):  
Zhen Yu ◽  
Lanting Liu ◽  
Kefei Wang ◽  
Hao Sun ◽  
Xiaojing We ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitor ◽  
Therapeutic Application

Novel Myeloma-Specific Multiple Peptides Able to Generate Cytotoxic T Lymphocytes: Potential Therapeutic Application in Multiple Myeloma and Other Plasma Cell Disorders,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3990-3990
Author(s):  
Jooeun Bae ◽  
Ruben Carrasco ◽  
Ann-Hwee Lee ◽  
Rao Prabhala ◽  
Yu-Tzu Tai ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Lymphocytes ◽  
Board Of Directors ◽  
Cytotoxic T Lymphocytes ◽  
Plasma Cell ◽  
Peptide Vaccine ◽  
Effector Memory ◽  
Therapeutic Application ◽  
Advisory Committees ◽  
Plasma Cell Disorders

Abstract Abstract 3990 Although single antigen targeted vaccination has been evaluated in multiple myeloma (MM), its efficacy has been limited. The major challenges in developing a MM-specific immunotherapy include heterogeneity of tumor associated antigens (TAA) expression, frequent mutations of specific TAA and variability of the human T-cell repertoire. We hypothesize that peptide vaccine efficacy may be enhanced by stimulating immune cells with multiple epitopes derived from different TAA. The goal of our study was to examine the effectiveness of a combination of four immunogenic HLA-A2-specific peptides derived from multiple MM-associated antigens to induce myeloma-specific cytotoxic T lymphocytes (CTL) ex vivo. The specific target antigens, XBP1, CD138 and CS1 play a significant role in MM pathogenesis. We have identified immunogenic HLA-A2-specific epitopes: heteroclitic XBP1 US184–192 (YISPWILAV), heteroclitic XBP1 SP367–375 (YLFPQLISV), native CD138260–268(GLVGLIFAV) and native CS1239–247 (SLFVLGLFL). In this study, first we evaluated each of the four epitopes in parallel and confirmed strong HLA-A2 binding affinity of the four individual peptides and demonstrated comparable phenotypes and overall functional activity of CTL generated with each peptide against HLA-A2+ MM cells. We next evaluated the multipeptide-specific CTL (MP-CTL) generated using a combination of all four peptides. The MP-CTL had an increased percentage of total CD8+ T cells, CCR7−CD45RO+(effector memory) and CD69+ (activated) cells. In addition, the MP-CTL demonstrated polyfunctional immune activities [higher IFN-g production, cell proliferation and cytotoxicity] against HLA-A2+ primary MM cells and MM cell lines, but not to HLA-A2− MM cells or HLA-A2+ breast cancer cells. Importantly, the MP-CTL demonstrated peptide-specific responses to all relevant epitopes including heteroclitic XBP1 US184–192 (YISPWILAV), heteroclitic XBP1 SP367–375 (YLFPQLISV), native CD138260–268(GLVGLIFAV) and native CS1239–247 (SLFVLGLFL), but not to an irrelevant CMV pp65 (NLVPMVATV) peptide in a various functional assays evaluated cytokine production and cytotoxicity. Moreover, the MP-CTL demonstrated similar or greater response against MM, compared to CTL generated using the individual peptides. Thus, targeting MM-associated antigens using a cocktail of specific peptides may provide an effective therapeutic application in patients with MM and related plasma cell disorders. Disclosures: Anderson: Celgene: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Munshi:Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees.

Proteasome inhibitors as therapeutics

2005 ◽  
Vol 41 ◽  
pp. 205-218
Author(s):  
Constantine S. Mitsiades ◽  
Nicholas Mitsiades ◽  
Teru Hideshima ◽  
Paul G. Richardson ◽  
Kenneth C. Anderson
Keyword(s):  
Multiple Myeloma ◽  
Drug Class ◽  
Proteasome Inhibitors ◽  
Cell Cycle Regulators ◽  
Current State ◽  
Intracellular Mechanism ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Hodgkin's Lymphomas ◽  
Clinical Research Data

The ubiquitin–proteasome pathway is a principle intracellular mechanism for controlled protein degradation and has recently emerged as an attractive target for anticancer therapies, because of the pleiotropic cell-cycle regulators and modulators of apoptosis that are controlled by proteasome function. In this chapter, we review the current state of the field of proteasome inhibitors and their prototypic member, bortezomib, which was recently approved by the U.S. Food and Drug Administration for the treatment of advanced multiple myeloma. Particular emphasis is placed on the pre-clinical research data that became the basis for eventual clinical applications of proteasome inhibitors, an overview of the clinical development of this exciting drug class in multiple myeloma, and a appraisal of possible uses in other haematological malignancies, such non-Hodgkin's lymphomas.

Bone sialoprotein mRNA and protein expression in human multiple myeloma cell lines and patients

2000 ◽  
Vol 111 (4) ◽  
pp. 1118-1121 ◽  
Author(s):  
A. Bellahcene ◽  
I. Van Riet ◽  
C. de Greef ◽  
N. Antoine ◽  
M. F. Young ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Protein Expression ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Bone Sialoprotein ◽  
Multiple Myeloma Cell ◽  
Human Multiple Myeloma ◽  
Mrna And Protein Expression

Continuous low-dose dexamethasone in relapsed or refractory multiple myeloma

2000 ◽  
Vol 111 (1) ◽  
pp. 381-381 ◽  
Author(s):  
C. W. Tiplady ◽  
G. P. Summerfield
Keyword(s):  
Multiple Myeloma ◽  
Low Dose ◽  
Refractory Multiple Myeloma
Sign in / Sign up

Export Citation Format

Share Document