Immunotherapy for COVID-19
1. There are no therapies available to treat COVID19.
2. Activated T and B lymphocytes for selective targeting of the virion.
3. Most effective for rapid onset of immunity to critical patients of COVID19.
Stimulation of an adaptive immune response is the most effective way to prevent infectious disease. Lymphocytes proliferate in response to antigen in peripheral lymphoid tissue. However this takes time. Immune responses that are generated can be either a T cell response or a B cell response. Adoptive transfer of B cell response or antibody response is being tried using convalescent plasma transfusion therapy from cured Covid-19 patients. In the proposed project we will try to use in-vitro activated T and B cells. T cells are needed to control intracellular pathogens and to activate B cell response to most immunogenic peptides. These T and B cells would then be transfused to generate adoptive T and B cell immunity. Cytotoxic T cells will kill the infected cell and antibodies generated from B cells will kill the free virus.
Covid-19 disease and associated ARDS is because of potential immune dysregulation and Cytokine Storm Syndrome. To overcome the lethal effects of the Cytokine storm, yet have a beneficial action of the activated T and B cells, we propose to grow the activated armed effector T and B cells in-vitro, assess their potential and then transfer them into patients.
The solution proposes to prime the body's own immune system to target the nCoV19. This cell therapy will first identify the immunogenic peptides in nCoV19 genome best suited to elicit an immune response from body's own immune cells. This is the bioinformatics part of the project. After identifying the peptides, they will be used to prime the dendritic cells in the body which help to elicit responses from T and B lymphocytes against the virus. The induced T and B cells will be selected and cultured and expanded in vitro, to be reinfused back into the patient as an infusion to treat COVID19.
1. Synthesis and validation of immunogenic peptide antigens capable of eliciting SARS-CoV-2 specific T and B cell response.
2. Banking of SARS-CoV-2 specific T and B cells for Adoptive Cell Immunotherapy for downstream characterization.
3. Preclinical validation of protocol for generating T and B cells recognizing SARS-CoV-2
The target population are the COVID19 patients in respiratory failure and with other serious manifestations of the disease. It serves the most critical of patients of COVID19, and offers a potential therapy for cure. The infusion works as a acute form of therapy that will lead to neutralisation of the virion and viral infected cells, and offer suppression of the ongoing infection.
The solution aims to be used by the doctors as a frontline therapy against COVID19 as it will be specific to the disease with little chance of cross reactivity with the normal body cells.
- Synthesis and validation of immunogenic peptide antigens capable of eliciting SARS-CoV-2 specific T and B cell response.
- Banking of SARS-CoV-2 specific T and B cells for Adoptive Cell Immunotherapy for downstream characterization.
- Preclinical validation of protocol for generating T and B cells recognizing SARS-CoV-2
- Concept: An idea being explored for its feasibility to build a product, service, or business model based on that idea
- A new application of an existing technology
Immunotherapy provides a effective and rapid way for gaining immunity against a specific antigen.
Activated lymphocytes
Adoptive T cell therapy has been tried out for specific antigens.
- Biotechnology / Bioengineering
- Children & Adolescents
- Elderly
- 3. Good Health and Well-Being
- India
- India
1. 0
2. POC
3. Thousands of patients in need of COVID19 immunity
1. Initial goal is to bioinformatically select the antigenic sequences that are best for eliciting antigenic response. This will then be used for isolation of DC cells and priming them with the selected antigenic sequences.
2. The T and B lymphocytes will be selected based on activation on coculture with dendritic cells. This will then be expanded in vitro for ultimately infusion into patients.
1. Technical hurdles- standardisation of lymphocytes expansion, the process of lymphocyte expansion for a clinically effective dose, the comorbidities that may limit dendritic cells and lymphocytes isolation
2. Financial- funding will be required for cell culture facility, though alomst all the machines are there, however, validation for cell culture, clean room certification according to GMP guidelines and cost for consummables will be required.
1. Close collaboration with working with CIIMS, hospital with MoU signed.
- For-profit, including B-Corp or similar models
1. Full time- 20
2. Part-time-10
3. Other workers- 5
Team members-
DR. SHAILENDRA MUNDHADA has studied and worked at the Immunology department of MD Anderson Cancer Center for 4 years from 1999 to 2003.
Dr Sheela Mundhada is transfusion medicine specialist and director of Jeevan Jyoti Blood Bank, Nagpur- a blood bank and component separation institute.
Dr Madhavi Deshmukh is microbiologist with experience in handling nCoV19 samples and processing for RTPCR test and successfully getting government regulatory approvals for handling and processing of nCoV19 samples.
Dr Aniruddha Mundhada has experience in working with adoptice cell therapy and in applying the technical knowhow in cell culture.
Dr. Rajpal Singh Kashyap has interest in vaccine development and diagnostic
kits. His lab experience of >15 years in working with different cell lines like THP1 - monocytic cell line for TB research. They also have vast experience in applied/ translational research and have received several funding from national (n=11), and international agencies (n=3) like DBT, DST, ICMR and CSIR & CMPDI.
DR. PRAMOD SUTRAVE, PhD, has worked as Scientist at the NCI, NIH, USA from 1983-96; Sigma, Kansas from 2004-05 and WRI, LLC, Briacell, Los Angeles USA as Chief Scientist from 2005-13. Dr. Pramod has a vast experience in research from the NIH to Private US firms. He will guide in designing the T and B cell assays. Both the partners are not legally bound or controlled by each other. They are known to each other because some common research interests and some earlier project proposals submitted.
CIIMS is a premier medical center in Central India based in Nagpur, with all specialties in one institute including research labs for bioinformatics and cell culture.
Central India Institute Of Medical Science
www.ciimsnagpur.com
We are also partnering with Jeevan Jyoti Blood Bank for transfusion services and knowhow in storage of blood and blood components.
Immuunotherapy as an infusion will be a product like a blood bag stored in blood banks after QC checks. The difference will be it will only be specific to one person whose cells have been harvested and expanded to be used as infusion.
- Organizations (B2B)
Service as infusion therapy will be overlaid with the cost of procuring consumables like cell culture media, cell isolation kits, bioinformatics resources.
Initially, we plan to get funds from trusts and the government for funding into research for viability of this approach and to generate a proof of concept.
We plan to then approach the government regulatory authorities for validation and certification. Clinical trials will require these permissions and we plan to ask for approval of these as a cell therpay or a gene product as it falls under these categories when applying for product license.
The product will be available as a infusion therapy at a one time cost. Also, if proven efficacious, it will be pitched to health insurance agencies as a therapy to be covered by their plans.
Solve provides a great platform to pitch for risky solutions to emerging problems like COVID19. The great network along with expertise reuqired for this approach is where Solve is very helpful. The leveraging of this expertise will allow for rapid testing and deployment of this concept as potential therapy for COVID19.
- Solution technology
- Funding and revenue model
The solution technology requires expertise in immunology and cell culture, and guidelines and SOPs to work in a lab. This expertise can be leveraged from the research labs that Solve and MIT have a collaboration with.
Also the funding and revenue model will have to be revised based on the costs involved in quality control and validation of these cell assays. There is a high chance of failure to grow these cells that will require a repeat harvest of the cells. This will ultimately affect the pricing and finances of the product. Here, MIT and Solve can help with speaking to investors and developing a revenue model that will offset some of these costs.
None of the current protocols being followed for Covid-19 treatment are definitive. Adoptively transferred
immunity mediated by T and B cells can provide immediate and also long lasting immunity. The goal is to
develop, grow and bank T and B cells for customized, precise and targeted Immunotherapy for Covid-19
patients.
Director (Research)