Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Antibody-based therapies in multiple myeloma.

ABSTRACT: The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies have largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA) approval of therapeutic Abs for cancer and other diseases.

SUBMITTER: Tai YT

PROVIDER: S-EPMC3200112 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Antibody-based therapies in multiple myeloma.

Tai Yu-Tzu YT Anderson Kenneth C KC

Bone marrow research 20110302

The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Alth ...[more]

PMID: 22046572

Similar Datasets

The development of potential antibody-based therapies for myeloma.

Project description:With optimal target antigen selection antibody-based therapeutics can be very effective agents for hematologic malignancies, but none have yet been approved for myeloma. Rituximab and brentuximab vedotin are examples of success for the naked antibody and antibody-drug conjugate classes, respectively. Plasma cell myeloma is an attractive disease for antibody-based targeting due to target cell accessibility and the complementary mechanism of action with approved therapies. Initial antibodies tested in myeloma were disappointing. However, recent results from targeting well-characterized antigens have been more encouraging. In particular, the CD38 and CD138 targeted therapies are showing single-agent activity in early phase clinical trials. Here we will review the development pipeline for naked antibodies and antibody-drug conjugates for myeloma. There is clear clinical need for new treatments, as myeloma inevitably becomes refractory to standard agents. The full impact is yet to be established, but we are optimistic that the first FDA-approved antibody therapeutic(s) for this disease will emerge in the near future.

| S-EPMC4482758 | biostudies-literature

Monoclonal Antibody Therapies in Multiple Myeloma: A Challenge to Develop Novel Targets.

Project description:The treatment options in multiple myeloma (MM) has changed dramatically over the past decade with the development of novel agents such as proteasome inhibitors (PIs); bortezomib and immunomodulatory drugs (IMiDs); thalidomide, and lenalidomide which revealed high efficacy and improvement of overall survival (OS) in MM patients. However, despite these progresses, most patients relapse and become eventually refractory to these therapies. Thus, the development of novel, targeted immunotherapies has been pursued aggressively. Recently, next-generation PIs; carfilzomib and ixazomib, IMiD; pomalidomide, histone deacetylase inhibitor (HDADi); panobinostat and monoclonal antibodies (MoAbs); and elotuzumab and daratumumab have emerged, and especially, combination of mAbs plus novel agents has led to dramatic improvements in the outcome of MM patients. The field of immune therapies has been accelerating in the treatment of hematological malignancies and has also taken center stage in MM. This review focuses on an overview of current status of novel MoAb therapy including bispecific T-cell engager (BiTE) antibody (BsAb), antibody-drug conjugate (ADC), and chimeric antigen receptor (CAR) T cells, in relapsed or refractory MM (RRMM). Lastly, investigational novel MoAb-based therapy to overcome immunotherapy resistance in MM is shown.

| S-EPMC6875016 | biostudies-literature

Emerging therapies for multiple myeloma.

Project description:Multiple myeloma (MM) is a clonal plasma cell malignancy clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. There are an estimated 750,000 people diagnosed with MM worldwide, with a median overall survival of 3 - 5 years. Besides chromosomal aberrations, translocations, and mutations in essential growth and tumor-suppressor genes, accumulating data strongly highlight the pathophysiologic role of the bone marrow (BM) microenvironment in MM pathogenesis. Based on this knowledge, several novel agents have been identified, and treatment options in MM have fundamentally changed during the last decade. Thalidomide, bortezomib, and lenalidomide have been incorporated into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM. Despite these significant advances, there remains an urgent need for more efficacious and tolerable drugs. Indeed, a plethora of preclinical agents awaits translation from the bench to the bedside. This article reviews the scientific rationale of new therapy regimens and newly identified therapeutic agents - small molecules as well as therapeutic antibodies - that hold promise to further improve outcome in MM.

| S-EPMC3183751 | biostudies-other

New therapies in multiple myeloma.

Project description:The melphalan-prednisone regimen has been considered as standard therapy for patients with multiple myeloma (MM) for many years. Recently, high-dose chemotherapy with stem-cell support has extended progression-free survival and increased overall survival, and it is now considered conventional therapy in younger patients. However, most patients relapse and the salvage treatment is not very effective. New active drugs, including immunomodulatory agents, thalidomide (Thal) and lenalidomide, and the proteasome inhibitor bortezomib, have shown promising anti-myeloma activity. These novel treatments are aimed at overcoming resistance of tumour cells to conventional chemotherapy, acting both directly on myeloma cells and indirectly by blocking the interactions of myeloma cells with their local microenvironment and suppressing growth and survival signals induced by autocrine and paracrine loops in the bone marrow. Thal has been widely studied, mostly in combination regimens in patients with relapsed MM and, more recently, in front-line therapy, showing efficacy in terms of response rate and event-free survival. Bortezomib has been found to possess remarkable activity, especially in combination with other chemotherapeutic agents, in relapsed/refractory and newly diagnosed MM, as well as in patients presenting adverse prognostic factors. Lenalidomide, in combination with dexamethasone, is showing high overall response rates in relapsed and refractory MM and promising results also in first-line therapy. In this paper, the results of the most significant trials with Thal, bortezomib and lenalidomide are reported. Several ongoing clinical studies will hopefully allow the identification of the most active combinations capable of improving survival in patients with MM.

| S-EPMC2779346 | biostudies-other

Immune-based therapies in the management of multiple myeloma.

Project description:Multiple myeloma (MM) is a clonal plasma cell malignancy affecting a predominantly elderly population. The continued development of newer therapies with novel mechanisms of action has reshaped the treatment paradigm of this disorder in the last two decades, leading to a significantly improved prognosis. This has in turn resulted in an increasing number of patients in need of therapy for relapsed/refractory disease. Immune-based therapies, including monoclonal antibodies, immune checkpoint inhibitors, and most promisingly, adoptive cellular therapies represent important therapeutic strategies in these patients due to their non-cross resistant mechanisms of actions with the usual frontline therapies comprising of immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). The anti-CD38 antibodies daratumumab and more recently isatuximab, with their excellent efficacy and safety profile along with its synergy in combination with IMiDs and PIs, are being increasingly incorporated in the frontline setting. Chimeric antigen receptor-T cell (CART) therapies and bi-specific T-cell engager (BiTE) represent exciting new options that have demonstrated efficacy in heavily pretreated and refractory MM. In this review, we discuss the rationale for use of immune-based therapies in MM and summarize the currently available literature for common antibodies and CAR-T therapies that are utilized in MM.

| S-EPMC7443188 | biostudies-literature

Promising therapies in multiple myeloma.

Project description: Not available

| S-EPMC4560339 | biostudies-literature

CD38 antibody re-treatment in daratumumab-refractory multiple myeloma after time on other therapies.

Project description:Monoclonal antibodies targeting CD38 are important for treatment of both newly diagnosed and relapsed multiple myeloma (MM). Daratumumab and isatuximab are anti-CD38 antibodies with the US Food and Drugs Administration approval in multiple different combinations. Despite good initial efficacy, patients inevitably develop drug resistance. Whether patients can be effectively re-treated with these antibodies in subsequent lines of therapy is unclear. Thus far, studies have mostly been limited to clinical retrospectives with short washout periods. To answer whether patients regain sensitivity after longer washouts, we used ex vivo sensitivity testing to isolate the anti-CD38 antibody-specific cytotoxicity in samples obtained from patients who had been exposed to and then off daratumumab for up to 53 months. MM cells from patients who had been off daratumumab for >1 year showed greater sensitivity than those with <1 year, although they still were less sensitive than those who were daratumumab naïve. CD38 expression on MM cells gradually recovered, although, again, not to the level of anti-CD38 antibody-naïve patients. Interestingly, low MM CD38 explained only 45% of cases identified to have daratumumab resistance. With clinical follow-up, we found ex vivo sensitivity predicted subsequent clinical response but CD38 overexpression did not. Patients clinically re-treated with anti-CD38 antibodies had <6 months of clinical benefit, but 1 patient who was daratumumab exposed but not refractory achieved complete response lasting 13 months. We conclude that transient efficacy can be achieved by waiting 1 year before CD38 antibody rechallenge, but this approach may be best used as a bridge to, or after, chimeric antigen receptor T-cell therapy.

| S-EPMC10598487 | biostudies-literature

CD38-Directed Therapies for Management of Multiple Myeloma.

Project description:The survival outcomes for multiple myeloma have improved several-fold in the past two decades, primarily due to the introduction of therapies with novel mechanisms of action including immunomodulatory agents, proteasome inhibitors, stem cell transplant and monoclonal antibodies in the schema of therapy. Antibody-based therapies targeting the surface marker CD38, namely daratumumab and isatuximab, have emerged as being highly effective as single agents as well as in combination regimens for both newly diagnosed and relapsed settings. Herein, the authors summarize the most recent data with both the current and emerging CD38-directed therapies in multiple myeloma.

| S-EPMC8254545 | biostudies-literature

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma.

Project description:Chimeric antigen receptor (CAR) T cells (CAR-T) have dramatically changed the treatment landscape of B-cell malignancies, providing a potential cure for relapsed/refractory patients. Long-term responses in patients with acute lymphoblastic leukemia and non Hodgkin lymphomas have encouraged further development in myeloma. In particular, B-cell maturation antigen (BCMA)-targeted CAR-T have established very promising results in heavily pre-treated patients. Moreover, CAR-T targeting other antigens (i.e., SLAMF7 and CD44v6) are currently under investigation. However, none of these current autologous therapies have been approved, and despite high overall response rates across studies, main issues such as long-term outcome, toxicities, treatment resistance, and management of complications limit as yet their widespread use. Here, we critically review the most important pre-clinical and clinical findings, recent advances in CAR-T against myeloma, as well as discoveries in the biology of a still incurable disease, that, all together, will further improve safety and efficacy in relapsed/refractory patients, urgently in need of novel treatment options.

| S-EPMC8327729 | biostudies-literature

Efficacy and Safety of Novel Agent-Based Therapies for Multiple Myeloma: A Meta-Analysis.

Project description:This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22-4.88] (P < 0.0001) for the novel agent-based regimens. These novel agent-based regimens showed greater benefit in terms of PFS of all subgroups irrespective of whether the patient received ASCT or not. The hazard ratio (HR) for PFS was 0.64 [95% CI: 0.60-0.69] (P < 0.00001). Improvements of OS could be found only in the bortezomib- and thalidomide-based regimens without ASCT. The pooled HRs were 0.74 [95% CI: 0.65-0.86] (P < 0.0001) and 0.80 [95% CI: 0.70-0.90] (P = 0.0004), respectively. Several AEs were shown more frequently in the novel agent-based regimens compared with controls such as hematologic events (neutropenia, anemia, and thrombocytopenia), gastrointestinal infection, peripheral neuropathy, thrombosis, and embolism events. In conclusion, in spite of the AEs, novel agent-based regimens are safe and effective for the treatment of MM.

| S-EPMC4753325 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data