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Posted On: 05/07/2020 11:48:08 AM
Post# of 148933
Still thinking about a solution for Sarah.....
On the other side we have again named Leronlimab here:
>>Leronlimab (PRO 140)
Leronlimab (CytoDyn) is an investigational humanized IgG4 monoclonal antibody against CCR5 receptors found on T lymphocytes. Chemokine receptor 5 (CCR5) was first characterized for its role as a co-receptor in human immunodeficiency virus (HIV) viral entry into white blood cells [55]. We now recognize that other pathogens, such as Dengue [56] or Staphylococcus aureus [57] also use the CCR5 signaling pathway for entry or as a virulence factor. Leronlimab is being repurposed and investigated as a treatment option for patients with COVID-19 who experience respiratory complications as a result of COVID-19. A single-arm, open-label, multi-center clinical study is set to take place to investigate the clinical improvement in total symptom score (i.e., fever, myalgia, dyspnea, and cough). Currently, leronlimab has a “fast-track” designation from the FDA for HIV and metastatic triple-negative breast cancer [58]. There are no serious side effects or adverse events reported so far. Leronlimab has successfully completed nine phase 1, 2, and 3 clinical trials in about 800 patients for other indications and achieved primary efficacy endpoints [59].
Reasoning by analogy with approved therapeutics in oncology, the acute toxicity from humanized antibodies can include (1) immunosuppression, predisposing to opportunistic infections or viral-induced neoplasias; (2) immunostimulation, including the dramatic “cytokine storm” of fevers, chills, myalgias, and acute lung injury similar to a severe presentation of COVID-19; and (3) hypersensitivity reactions [60]. The specificity of antibodies is likely to give rise to idiosyncratic side effect profiles and not all antibodies will cause the same degree of immunosuppression or immune cell activation.
We expect humanized antibodies to be less likely to cause serum sickness than antibodies raised in horse (i.e., Anavip) or raised in sheep (i.e., CroFab). Anavip (Rare Disease Therapeutics, Inc.) and CroFab (Protherics Inc.) are antibody therapies used to treat envenomation by North American crotalids. A humanized antibody is an antibody raised from non-human species and then modified to increase its similarity to naturally occurring human antibodies so as to provoke less of a humoral immune response in humans. For example, antibodies raised in mice can have their Fc region replaced by human sequences to decrease immunogenicity [61]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192319/
On the other side we have again named Leronlimab here:
>>Leronlimab (PRO 140)
Leronlimab (CytoDyn) is an investigational humanized IgG4 monoclonal antibody against CCR5 receptors found on T lymphocytes. Chemokine receptor 5 (CCR5) was first characterized for its role as a co-receptor in human immunodeficiency virus (HIV) viral entry into white blood cells [55]. We now recognize that other pathogens, such as Dengue [56] or Staphylococcus aureus [57] also use the CCR5 signaling pathway for entry or as a virulence factor. Leronlimab is being repurposed and investigated as a treatment option for patients with COVID-19 who experience respiratory complications as a result of COVID-19. A single-arm, open-label, multi-center clinical study is set to take place to investigate the clinical improvement in total symptom score (i.e., fever, myalgia, dyspnea, and cough). Currently, leronlimab has a “fast-track” designation from the FDA for HIV and metastatic triple-negative breast cancer [58]. There are no serious side effects or adverse events reported so far. Leronlimab has successfully completed nine phase 1, 2, and 3 clinical trials in about 800 patients for other indications and achieved primary efficacy endpoints [59].
Reasoning by analogy with approved therapeutics in oncology, the acute toxicity from humanized antibodies can include (1) immunosuppression, predisposing to opportunistic infections or viral-induced neoplasias; (2) immunostimulation, including the dramatic “cytokine storm” of fevers, chills, myalgias, and acute lung injury similar to a severe presentation of COVID-19; and (3) hypersensitivity reactions [60]. The specificity of antibodies is likely to give rise to idiosyncratic side effect profiles and not all antibodies will cause the same degree of immunosuppression or immune cell activation.
We expect humanized antibodies to be less likely to cause serum sickness than antibodies raised in horse (i.e., Anavip) or raised in sheep (i.e., CroFab). Anavip (Rare Disease Therapeutics, Inc.) and CroFab (Protherics Inc.) are antibody therapies used to treat envenomation by North American crotalids. A humanized antibody is an antibody raised from non-human species and then modified to increase its similarity to naturally occurring human antibodies so as to provoke less of a humoral immune response in humans. For example, antibodies raised in mice can have their Fc region replaced by human sequences to decrease immunogenicity [61]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192319/
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