Bispecific monoclonal antibodies for targeted immunotherapy of solid tumors: Recent advances and clinical trials

: Monoclonal antibodies are one of the most eminent types of immunotherapeutics that have taken over the biopharmaceutical market because they are approved for a wide range of cancers, either blood-based malignancies or solid tumors, and also non-cancer indications, from migraine to viral infections. Due to their wide applicability as immunotherapeutics, countless biopharmaceutical companies try to be in the competition by developing monoclonal antibodies and advancing into clinical trials with them. Since the approval of the first monoclonal antibodies, the speed of their discovery and approval for medical use have been rather incremental, so that the progress of this market has been anticipated to increase in the current decade. Herein, we take a look at some of the monoclonal antibodies, which have been approved for clinical use in the current decade, so far. Moreover, we underline the encouraging results from the clinical trials that led to the approval of these immunotherapeutics.

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Antibody Therapy for the Control of Viral Diseases: An Update

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190809112704 ◽

2019 ◽

Vol 20 (13) ◽

pp. 1108-1121 ◽

Cited By ~ 7

Author(s):

Miriam Dibo ◽

Eduardo C. Battocchio ◽

Lucas M. dos Santos Souza ◽

Matheus D. Veloso da Silva ◽

Bruna K. Banin-Hirata ◽

...

Keyword(s):

Clinical Trials ◽

Monoclonal Antibodies ◽

Viral Antigen ◽

Viral Infections ◽

Antibody Therapy ◽

Therapeutic Strategies ◽

Viral Diseases ◽

Specific Antibodies ◽

The Status ◽

Epidemiological Impact

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

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A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

Current Drug Targets ◽

10.2174/1389450121666200727121011 ◽

2020 ◽

Vol 21 ◽

Author(s):

Daniel Sur ◽

Andrei Havasi ◽

Alecsandra Gorzo ◽

Claudia Burz

Keyword(s):

Colorectal Cancer ◽

Drug Resistance ◽

Clinical Trials ◽

Monoclonal Antibodies ◽

Metastatic Colorectal Cancer ◽

Second Generation ◽

Current Data ◽

Braf Mutations ◽

Durable Response ◽

Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

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Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development

Antibodies ◽

10.3390/antib8020034 ◽

2019 ◽

Vol 8 (2) ◽

pp. 34 ◽

Cited By ~ 4

Author(s):

Ahmad Iftikhar ◽

Hamza Hassan ◽

Nimra Iftikhar ◽

Adeela Mushtaq ◽

Atif Sohail ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Monoclonal Antibodies ◽

Combination Therapy ◽

Immune Responses ◽

Web Of Science ◽

Cochrane Library ◽

Future Perspectives ◽

Antibody Drug Conjugate ◽

Chemotherapy Agents

Background: Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with lenalidomide (Len) and dexamethasone (Dex), producing a clinical benefit rate (CBR) of 83%. Additionally, Isa used in combination with pomalidomide (Pom) and Dex resulted in a CBR of 73%. Indatuximab Ravtansine (anti-CD138 antibody-drug conjugate) produced an ORR of 78% and 79% when used in combination with Len-Dex and Pom-Dex, respectively. Conclusions: Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted.

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Progression-Free Survival as a Surrogate for Overall Survival in Clinical Trials of Targeted Therapy in Advanced Solid Tumors

Drugs ◽

10.1007/s40265-017-0728-y ◽

2017 ◽

Vol 77 (7) ◽

pp. 713-719 ◽

Cited By ~ 14

Author(s):

Stefan Michiels ◽

Everardo D. Saad ◽

Marc Buyse

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Targeted Therapy ◽

Solid Tumors ◽

Progression Free Survival ◽

Advanced Solid Tumors ◽

Free Survival

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Prediction of Clearance of Monoclonal and Polyclonal Antibodies and Non-Antibody Proteins in Children: Application of Allometric Scaling

Antibodies ◽

10.3390/antib9030040 ◽

2020 ◽

Vol 9 (3) ◽

pp. 40

Author(s):

Iftekhar Mahmood

Keyword(s):

Clinical Trials ◽

Monoclonal Antibodies ◽

Prediction Error ◽

Allometric Scaling ◽

Polyclonal Antibodies ◽

Therapeutic Proteins ◽

Preterm Neonates ◽

Pharmacokinetic Parameters ◽

Pediatric Dose ◽

Age Dependent

Allometric scaling can be used for the extrapolation of pharmacokinetic parameters from adults to children. The objective of this study was to predict clearance of therapeutic proteins (monoclonal and polyclonal antibodies and non-antibody proteins) allometrically in preterm neonates to adolescents. There were 13 monoclonal antibodies, seven polyclonal antibodies, and nine therapeutic proteins (non-antibodies) in the study. The clearance of therapeutic proteins was predicted using the age dependent exponents (ADE) model and then compared with the observed clearance values. There were in total 29 therapeutic proteins in this study with 75 observations. The number of observations with ≤30%, ≤50%, and >50% prediction error was 60 (80%), 72 (96%), and 3 (4%), respectively. Overall, the predicted clearance values of therapeutic proteins in children was good. The allometric method proposed in this manuscript can be used to select first-in-pediatric dose of therapeutic proteins in pediatric clinical trials.

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