Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug-Resistant HIV-1 Infection

Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents on the market. To date, approximately 80 mAbs have been granted marketing approval. In 2018, 12 new mAbs were approved by the FDA, representing 20% of the total number of approved drugs. The majority of mAb therapeutics are for oncological and immunological/infectious diseases, but these are expanding into other disease areas. Over 100 monoclonal antibodies are in development, and their unique features ensure that these will remain a part of the therapeutic pipeline. Thus, the therapeutic value and the elucidation of their pharmacological properties supporting clinical development of these large molecules are unquestioned. However, their utilization as pharmacological tools in academic laboratories has lagged behind their small molecule counterparts. Early therapeutic mAbs targeted soluble cytokines, but now that mAbs also target membrane‐bound receptors and have increased circulating half‐life, their pharmacology is more complex. The principles of pharmacology have enabled the development of high affinity, potent and selective small molecule therapeutics with reduced off‐target effects and drug‐drug interactions. This review will discuss how the same basic principles can be applied to mAbs, with some important differences. Monoclonal antibodies have several benefits, such as fewer off‐target adverse effects, fewer drug‐drug interactions, higher specificity, and potentially increased efficacy through targeted therapy. Modifications to decrease the immunogenicity and increase the efficacy are described, with examples of optimizing their pharmacokinetic properties and enabling oral bioavailability. Increased awareness of these advances may help to increase their use in exploratory research and further understand and characterize their pharmacological properties.

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“…28 Another example is ibalizumab (Trogarzo), approved in 2018 for the treatment of multidrug-resistant HIV-1 infection. 29…”

Section: Leading To the Interactions Betweenmentioning

confidence: 99%

The pharmacology and therapeutic applications of monoclonal antibodies

Castelli

McGonigle

Hornby

2019

Pharmacology Res & Perspec

159

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“…Maraviroc is a US FDA and European Medicines Agency (EMA)-approved novel small molecule that blocks gp120 interaction with CCR5 with potent anti-HIV activity (Xu et al 2014 ). Ibalizumab (Trogarzo), a monoclonal antibody binds to the CD4 receptor and blocks its interaction with gp120, and inhibits HIV entry which was also approved by FDA (Beccari et al 2019 ).…”

Section: Viral Fusion Proteinsmentioning

confidence: 99%

Entry Inhibitors: Efficient Means to Block Viral Infection

Pattnaik

Chakraborty

2020

J Membrane Biol

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“…Ibalizumab-It is a humanized monoclonal antibody which acts by impeding the conformational change in CD4 -gp120 complex causing post attachment inhibition by a stearic hindrance to stop interaction of CCRX4 and CCRX 5 with gp120 and causes rearrangement of gp41 to inhibit fusion of viral particle. 37 Leronlimab-It is an anti CCR5 monoclonal antibody active against HIV -1 virus. 38 It is seen that Leronlimab act synergistically with other small molecule CCR5 inhibitors with the first causing competitive inhibition and other causing allosteric inhibition which can lay a path for novel combination for resistant HIV treatment.…”

Section: Broadly Neutralizing Monoclonal Antibodies (Bnabs)-mentioning

confidence: 99%

A Concise Review of Existing Therapies and Recent Advances in the Management of HIV Infection

Lal¹,

Kumar²,

Dutta³

et al. 2020

IJPSRR

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Human immunodeficiency virus (HIV) is an RNA retrovirus capable of replicating its genome by the DNA dependent RNA polymerase (DdRp). The virus infects the lymphocytes with the help of viral glycoproteins like Gp 120 and Gp 41. The entry of virus leads to the release of viral RNA inside the host cell, which is further replicated, and assembly of virion particles leads to the release of viral particles that further infect the other host cells. Established therapies include those that inhibit the entry of virus in the host cell, those inhibiting the integrase activity, those acting as protease inhibitors and also we have Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside reverse transcriptase inhibitors (NNRTIs) with NRTIS being the competitive inhibitors of DdRp also show mitochondrial toxicity. Protease inhibitors are known for their adverse effect profile and several drug interactions due to their enzyme inhibitory property. The most effective approach in the management is the highly active antiretroviral therapy containing the combined use of drugs having varied mechanisms of action. Still, long term use of these agents can end up in resistance against these agents. Well documented adverse effect profile along with various drug interactions associated with anti-HIV drugs mandates the need for the development of newer drugs against HIV. Newer molecules provide a better safety profile and better alternatives for drug-resistant cases. Therefore, this review focuses on existing therapies along with various newer pipeline drugs with their mechanisms and advantages over the existing therapies.

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Ibalizumab, a Novel Monoclonal Antibody for the Management of Multidrug-Resistant HIV-1 Infection

Cited by 63 publications

References 29 publications

The pharmacology and therapeutic applications of monoclonal antibodies

The pharmacology and therapeutic applications of monoclonal antibodies

Entry Inhibitors: Efficient Means to Block Viral Infection

A Concise Review of Existing Therapies and Recent Advances in the Management of HIV Infection

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