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HCFI Round Table Expert Zoom Meeting on “Monoclonal antibodies in COVID-19”

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#Multispeciality 

Dr Veena Aggarwal, Consultant Womens’ Health, CMD and Editor-in-Chief, IJCP Group & Medtalks Trustee, Dr KK’s Heart Care Foundation of India    22 November 2021

Speaker: Prof Dr Arun Jamkar, Ex Vice Chancellor Maharashtra University of Health Sciences Nashik, Technical consultant Persistent Systems Ltd, Chief Medical Officer Indx Technology, Distinguished Professor SIU Pune

13th November, 2021; 11am-12noon

Key points of HCFI Expert Round Table

  • Where epitopes and receptor interactions are known and valid, monoclonal antibodies work. In Covid, the exact pathogenesis is still not well-understood.
  • Kohler and Milstein provided the most outstanding proof of clonal selection theory by fusion of normal and malignant cells (Hybridoma technology) for which they were awarded the Nobel Prize in 1984.
  • Transplant rejections were improved after the introduction of the first monoclonal antibody OKT3 in 1986. It was FDA approved for preventing kidney transplant rejection.
  • The steps of preparation of antibodies are immunize animal, isolate spleen cells (containing antibody producing B cell), fuse spleen cells with myeloma cells (using PEG), allow unfused B cells to die, add aminopterin to culture and kill unfused myeloma cells, clone remaining cells, screen supernatant of each clone for presence of desired antibody, grow chosen clone of cells in tissue culture indefinitely and harvest antibody from the culture.
  • Nomenclature of monoclonal antibodies: If it is murine, it is called “omab”; if it is chimeric but still human, it is called “ximab” and once it is humanised (>60%), it is called “zumab”. When it is fully humanised, it is called “umab”.
  • Monoclonal antibodies prevent viral binding and/or fusion with host cell. They bind to the spike protein, prevent the virus from attaching to human cells and tag it for destruction preventing the development of severe Covid-19.
  • Tocilizumab was one of the most successful drugs in managing cytokine storm, which is a lethal event in Covid-19 and is mediated through IL-6 and TNF-alpha.
  • In a meta-analysis of 16 randomized-controlled trials, tocilizumab reduced mortality risk in severe to critical disease and lowered mechanical ventilation requirements. It also facilitated hospital discharge.
  • If monoclonal antibodies are given within 7 days of getting the infection, they are most successful. It does not allow the virus to attach to the cell. Hence, it can be a game changer in the treatment of Covid. Only symptomatic patients – mild or moderate - can be given monoclonal antibodies.
  • Casirivimab and imdevimab antibody cocktail was used in India for the first time in Medanta hospital.
  • There are around 75 monoclonal antibodies available today in various stages of development. Many of them are in phase III trial.
  • Bamlanivimab + etesevimab and casirivimab +imdevimab reduce viral load when given early on in the course of the infection and favorably impact clinical outcomes in patients with mild to moderate disease.
  • Bamlanivimab + etesevimab bind to different but overlapping epitopes in the spike protein RBD of SARS-CoV-2. Their distribution was paused in the US because both the gamma and beta variants have reduced susceptibility to Bamlanivimab + etesevimab. But distribution has been reinstated in states with low rates of these variants.
  • The FDA issued EUA for treatment of mild to moderate Covid-19 in adults and children ≥12 years weighing ≥40 kg and who are at high risk for progressing to severe disease and/or hospitalization. It is given as IV infusion (casirivimab 600 mg + imdevimab 600 mg). Subcutaneous injection is an alternative route. It is to be administered as soon as possible after a positive RT PCR and within 10 days of symptom onset in high-risk patients.
  • Bamlanivimab + etesevimab is not yet available in India.
  • According to an observational study from Pune, combination therapy of tocilizumab and steroids is likely to be safe and effective in the management of Covid-19 associated cytokine release syndrome.
  • The 2018 Nobel Prize in Physiology or Medicine was awarded to James Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation. Inhibition of these molecules by immune checkpoint inhibitors can successfully activate the immune system to fight cancer.
  • The immune checkpoint inhibitors act by blocking checkpoint proteins (CTLA-4) from binding with their partner proteins. This prevents the “off” signal from being sent, allowing the T cells to kill cancer cells.
  • Anti-CTLA-4 opened a new field called immune checkpoint therapy.
  • Ipilimumab blocks the CTLA-4 checkpoint protein. Pembrolizumab and nivolumab target the PD-1, while atezolizumab target the PD-L1 protein.
  • Cancer is disease of genome. In a survey of oncologists from the US, overall, 75% reported using NGS tests to guide treatment decisions.
  • Monoclonal antibodies can be used not only in cancer, but also in rheumatoid arthritis,
  • Challenges to the use of monoclonal antibodies are diversity of the virus, bioavailability in the lungs (most commonly affected organ).
  • A larger clinical trial needs to be done with the support of the government.
  • We need to find out which receptors are being used for monoclonal antibodies and which action has to be stopped. We are studying the results of the pathogenesis and not the origin and trigger of the pathogenesis.
  • Monoclonal antibodies are costly and have to be administered under supervision. Infectious disease specialists at the tertiary center can supervise doctors at the periphery (community health center).

Participants

Dr KK Kalra

Dr Ashok Gupta

Dr Suneela Garg

Dr DP Lokwani

Dr Arun Jamkar

Dr Milind Deshpande

Ms Ira Gupta

Dr S Sharma

Moderator

Mr Saurabh Aggarwal

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