Researchers have already completed the first phase of the exploratory toxicology study in animals and the results seem encouraging
One good outcome from the ongoing COVID-19 crisis is that the Indian scientific communities have all put on their thinking hats and have begun investing in productive research in the field of infectious diseases. One among these many research activities in discussion lately has been the development of anti-COVID cytokine concoction by HCG’s research team along with iCrest-the immunology wing of HCG and assisted by Elseviers Resouce Centre.
Influenced by the philosophy of Sun Tzu in the ‘Art of War’ who teaches about peacefully resolving conflict, these key cancer researchers comprising Dr Jyothsna Rao, an immunologist; Dr Gururaj Rao, a molecular and cell biologist and Dr US Vishal Rao, an oncologist, believe that silent yet powerful treatment technique can save the lives of millions.
The research and its ideology
Interestingly, this research stems from the idea of treating various cancers using immunotherapy. It involves stimulating the immune response to trigger Interferons (IFN) production at the very early stages of the disease. Researchers have already completed the first phase of the exploratory toxicology study in animals and the results seem encouraging. Therefore, work for the second stage has begun.
Encouraged by the initial success of this research, Dr Ajaikumar, MD and CEO, HCG, shares, “India should be at the forefront of research and make an active contribution to the understanding and solving of this pandemic. This is the time when the best brains can come together and make a sincere attempt towards creating a difference to humanity. At HCG, we have been working on onco- virology. Viruses are the cause of approximately 15 per cent of human cancers. The study of tumour viruses has led to important discoveries in cancer research. We thought this was an appropriate time for our immunology, cell biology and haematology team to contribute to the pandemic. Elsevier’s publication team has continually provided valuable inputs through the resource centre to keep our scientific rigour and momentum. We have been in talks with various universities abroad like Emory University, Atlanta exchanging scientific progress and taking valuable inputs. They have expressed interest to collaborate in an endeavour to find tangible therapeutic targets against the virus.”
How the immune-response therapy works
The treatment technique simply involves stimulating the immune responses in the early stages of COVID-19. They have made a concoction of cytokines – IF-gamma, along with cytokines which are released by our immune system against the virus attack and have been known to be effective against COVID-19 too. Unfortunately, patients infected with corona virus are unable to produce them. The researchers have activated T cells from healthy donors, in a cGMP facility at iCrest – HCG hospital with an enriched cocktail of cytokines rich in Interferons (IFN). According to these researchers, interferon is a treatment for this type of viral infection, and they believe using this immune-modular can save many lives.
They will hopefully create the first set of injections soon for patient use. The team has already written to the Drug Controller General of India (DCGI) and hope to get the initial clearance for expedited review with support from the Indian Council of Medical Research (ICMR) and the Government of India.
Expounding further on the rationale of the research work, Dr Vishal Rao, Director – Head Neck Surgical Oncology and Robotic Surgery Associate Dean – Centre of Academics and Research HealthCare Global (HCG) Cancer Centre informs, “We have 10 types of immune cells at the least that are widely dispersed in millions across the body. When our body is invaded by a foreign organism (bacteria, fungi or virus), these cells work with each other to destroy the invader. Now, the question is – how do the immune cells talk to each other? They use small-molecule substances called cytokines (Cyto-Cells; Kine – movement). There are many cytokines that are involved in work on the immune system. The most relevant for viruses are interferons.”
Interferons, as the name reflects, can interfere with the viral activity and stop their multiplication. These specialised signal proteins are released by our cells in response to a viral attack to forewarn other cells. They help build the anti-viral proteins within the cells to kill the virus as it tries to invade the new cells. Historically, interferons are a group of cytokines known to be potent anti-viral agents against viruses and a hallmark cytokine induced by the host upon viral infections. Interferons possess unique immuno-regulatory activities and are signature cytokines released by (TH1) T immune cells, which are crucial in viral infections.
“In patients infected with coronavirus, it was indicated that the activation of the IFN does not occur until 48 hours post-infection. Thus, the delayed IFN-related anti-viral response by the healthy cells leads to coronavirus evading the immune response. Numerous studies have presented the success in defeating CoVs by the direct administration of IFNs. In combination as concoction, it was shown to synergistically inhibit the virus replication in vitro. Moreover, it is understood that the earlier induction of IFNs in children, although they have a less developed immune system, could be the reason behind them being least affected. The key to success in reducing the disease fatality might be the stimulation of the immune responses to trigger IFN production at the very early stages of the disease, which might be done through the administration of IFN. Despite the evidence for the efficacy of IFNs in treating CoV-induced infections, the proper dosing and ideal timing for such interventions need to be verified in clinical trials”, Dr Rao adds.
For the later stages of the diseases or in advance stages where patients are on the ventilator and have developed respiratory distress, these researchers propose to utilise the mesenchymal cells derived from donor bone marrow that has been known to treat the acute respiratory syndrome. Mesenchymal cells are known to possess anti-inflammatory activity and thus used often in autoimmune diseases.
Approvals and recognitions awaited
Informing about the approvals and the ICMR and government’s response to this research, Dr Ajaikumar informs, “We await instruction from DCGI and ICMR. We have also submitted the concept to an international journal. The Karnataka government has already given a letter of support and will be assisting us.”
While the DCGI and the ICMR are currently occupied in the various response actions and approval of several innovations, the officials were not in the capacity to comment on the relevance of this research. However, the scrutiny is underway, informed the officials. Nevertheless, they further mentioned that the government will encourage every research and effort taken in the right direction which will not only be beneficial to combat this current pandemic, but to avert future outbreaks as well.
The relevance of this research
According to Cancer Research Institute, insights gained from decades of scientific research on our immune system and how it responds to infectious disease and cancer are not only helping to inform treatment for COVID-19 today, but may also lead to strategies to prevent future outbreaks of the virus.
So, how will this be different from a vaccine?
Preventive vaccines work by teaching the immune system to recognise specific threats before encountering them—in this case, COVID-19. In the case of the above-mentioned immuno-modulator, this can be utilised as a treatment protocol as and when the clinical trials achieve the desired medical outcomes and success.
Also, as pointed out by the Cancer Research Institute, such research holds the key to unlock solutions and strategies in detection and prevention of infectious diseases as well as fend off future outbreaks.
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