scholarly journals Role of Bispecific antibody for Multiple Myeloma; A literature Review

2021 ◽  
pp. 1-4
Author(s):  
Madeeha Subhan Waleed ◽  
Keyword(s):  
Multiple Myeloma ◽  
Binding Sites ◽  
Bispecific Antibody ◽  
Organ Damage ◽  
Bispecific Antibodies ◽  
Efficacy And Safety ◽  
Potential Benefits ◽  
Wide Group ◽  
New Treatments

Multiple myeloma (MM), as defined by a clonal plasma cell proliferation, manifests as end organ damage caused by the abnormally high monoclonal paraprotein.In this article, we have reviewed the potential benefits of Bispecific antibodies (BsAbs) in MM patients. In addition, new BsAbs developments and clinical trials for various MM targets are discussed in detail. Bispecific antibodies are the types of antibodies that have two different antigen binding sites in one molecule. There are 100 different classes of BsAb and all these can be divided into 2 main categories based on their fragments and both categories are under trials for MM.Despite some studies showing adverse effects development of these new treatments is going to greatly contribute to improve outcomes for a wide group of patients which also requires further clinical studies to be conducted with focus on demonstration of efficacy and safety profile.

scholarly journals Ubiquitination and Ubiquitin-Like Modifications in Multiple Myeloma: Biology and Therapy

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3764
Author(s):  
Matthias Wirth ◽  
Markus Schick ◽  
Ulrich Keller ◽  
Jan Krönke
Keyword(s):  
Multiple Myeloma ◽  
Translational Regulation ◽  
Proteasome Inhibitors ◽  
Ubiquitin Proteasome System ◽  
Organ Damage ◽  
Post Translational Modifications ◽  
Damage Repair ◽  
Ubiquitin Proteasome ◽  
New Treatments ◽  
Effective Drugs

Multiple myeloma is a genetically heterogeneous plasma cell malignancy characterized by organ damage and a massive production of (in-)complete monoclonal antibodies. Coping with protein homeostasis and post-translational regulation is therefore essential for multiple myeloma cells to survive. Furthermore, post-translational modifications such as ubiquitination and SUMOylation play key roles in essential pathways in multiple myeloma, including NFκB signaling, epigenetic regulation, as well as DNA damage repair. Drugs modulating the ubiquitin–proteasome system, such as proteasome inhibitors and thalidomide analogs, are approved and highly effective drugs in multiple myeloma. In this review, we focus on ubiquitin and ubiquitin-like modifications in the biology and current developments of new treatments for multiple myeloma.

The Role of FOLFIRINOX in Advanced Pancreatic Cancer: A Meta-analysis

2021 ◽  
Author(s):  
Nannan Du ◽  
Fengyan Zhou ◽  
Jiaze Hong ◽  
Derry Minyao Ng ◽  
Tong Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
White Blood Cells ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Hematological Toxicity ◽  
Efficacy And Safety ◽  
Potential Benefits

Abstract BackgroundThe prognosis of pancreatic cancer (PC) is extremely poor and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC.MethodsWe searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from their inception to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS).ResultsWe found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR: 0.76, 95% Cl: 0.67-0.86, p<0.001), but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than mono-chemotherapy (HR: 0.59, 95% Cl: 0.52-0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR: 0.76, 95% Cl: 0.61-0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR: 0.91, 95% Cl: 0.82-1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea.ConclusionThese findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors.

Development of a fully human T cell engaging bispecific antibody for the treatment of multiple myeloma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8017-8017 ◽  
Author(s):  
Ben Buelow ◽  
Duy Pham ◽  
Starlynn Clarke ◽  
Shelley Force Aldred ◽  
Kevin Dang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Bispecific Antibody ◽  
Plasma Cells ◽  
Bispecific Antibodies ◽  
Human Pbmcs

8017 Background: Although BCMA is a plasma cell specific surface molecule attractive as an antibody target in multiple myeloma, its scarcity on the cell surface may limit the efficacy of a conventional antibody. T-cell engaging bispecific antibody approaches are highly efficacious and are particularly well suited for a membrane target with limited expression, such as BCMA. Teneobio has developed a multivalent antibody platform based on modular human VH domains, which allowed us to build T cell engaging bispecific antibodies with low and high T cell agonistic activities. Methods: UniRats were immunized with either CD3 or BCMA antigens and antigen-specific UniAbs were identified by antibody repertoire sequencing and high-throughput gene assembly, expression, and screening. High affinity binding VH sequences were selected using recombinant proteins and cells. In vitro efficacy studies included T-cell activation by cytokine- and tumor cell kill by calcein-release assays. In vivo efficacy of the molecules was evaluated in NSG mice harboring myeloma cells and human PBMCs. Results: BCMA-specific UniAbs bound plasma cells with high affinities (100-700pM) and cross-reacted with cynomolgus plasma cells. Strong and weak T cell agonists were identified that bound human T cells with high and low affinities respectively and cross-reacted with cynomolgus T cells. T cell engaging bispecifics with a strong (H929 cytotoxicity:EC50=27pM) and a weak T cell activating arm (H929 cytotoxicity: EC50=1170pM) demonstrated T-cell activation and tumor-cell cytotoxicity in vitro; bispecifics with a weak CD3 engaging arm showed markedly reduced cytokine production even at doses saturating for cytotoxicity. In viv o, BCMAxCD3 bispecific antibodies reduced tumor load and increased survival when co-administered with human PBMCs as compared to controls. Conclusions: Our results suggest that T cell engaging bispecifics with low-affinity anti-CD3 arms could be preferred for the treatment of Multiple Myeloma.

scholarly journals Current and emerging immunotherapeutic approaches to the treatment of multiple myeloma

2019 ◽  
Vol 10 ◽  
pp. 204062071985417
Author(s):  
Dawn Swan ◽  
Kevin Lynch ◽  
Mark Gurney ◽  
Michael O’Dwyer
Keyword(s):  
Multiple Myeloma ◽  
Immune System ◽  
Immune Evasion ◽  
Proteasome Inhibitors ◽  
Standard Of Care ◽  
Bispecific Antibodies ◽  
Clinical Use ◽  
Immunomodulatory Drugs ◽  
Care Regimes

Multiple myeloma (MM) has a worldwide incidence of 1–5/100,000/year. Outcomes have improved significantly in recent years following incorporation of immunomodulatory drugs and proteasome inhibitors into standard-of-care regimes. MM is profoundly immunosuppressive, enabling immune evasion, proliferation and disease progression. The role of the immune system in MM is becoming increasingly characterized and understood, and numerous therapies are under development or in routine clinical use targeting these elements of MM pathogenesis. In this review we discuss the immunosuppressive effects of MM, then the therapies targeting these defects. Specifically, we review the monoclonal and bispecific antibodies, alongside adoptive cellular therapies currently under investigation.

scholarly journals Potential Role of CD47-Directed Bispecific Antibodies in Cancer Immunotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Yang ◽  
Zheng Yang ◽  
Yun Yang
Keyword(s):  
Cancer Immunotherapy ◽  
Potential Role ◽  
Bispecific Antibody ◽  
Lymphoblastic Leukemia ◽  
Bispecific Antibodies ◽  
The Novel ◽  
Mechanisms Of Resistance ◽  
Immunological Therapy ◽  
Novel Targets

The prosperity of immunological therapy for cancer has aroused enormous passion for exploiting the novel targets of cancer immunotherapy. After the approval of blinatumomab, a bispecific antibody (bsAb) targeting on CD19 for acute lymphoblastic leukemia, a few of CD47-targeted bsAbs for cancer immunotherapy, are currently in clinical research. In our review of CD47-targeted bsAbs, we described the fundamental of bsAbs. Then, we summarized the information of four undergoing phase I researches, reviewed the main toxicities relevant to CD47-targeted bsAb immunological therapy of on-target cytotoxicity to healthy cells and a remarkable antigen-sink. Finally, we described possible mechanisms of resistance to CD47-targeted bsAb therapy. More clinical researches are supposed to adequately confirm its security and efficacy in clinical practice.

scholarly journals The role of FOLFIRINOX in metastatic pancreatic cancer: a meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Beilei Zhang ◽  
Fengyan Zhou ◽  
Jiaze Hong ◽  
Derry Minyao Ng ◽  
Tong Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
White Blood Cells ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Hematological Toxicity ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Potential Benefits

Abstract Background The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC. Methods We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS). Results We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, p<0.001) but had no benefit on PFS. Results from subgroup analyses showed that FOLFIRINOX had superior benefits than monochemotherapy (HR 0.59, 95% Cl 0.52–0.67, p<0.001), followed by FOLFIRINOX versus combination chemotherapy (HR 0.76, 95% Cl 0.61–0.95, p<0.001). The result of FOLFIRINOX versus nab-paclitaxel + gemcitabine had no benefit (HR 0.91, 95% Cl 0.82–1.02, p>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea. Conclusion These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors. Graphical abstract

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