Pipeline Of Products Under Development

Cellf is developing innovative methods to treat COVID 19. We have three programs in early stage development cantered around three different theories , each of which are under trial approved by Indian Council of Medical Research and Central Drugs standard control organisation. Our carefully selected programs involve disease areas in which CELLF management team has significant expertise, where there is a recognized significant unmet medical need and where we believe we can compete effectively.

Mesenchymal cell therapy for COVID 19 patients

Mesenchymal cell therapy is a new approach to improve patient’s biological resistance to COVID 19. Remarkably, gene expression profiles of the recovered Mesenchymal cell therapy showed high anti-inflammatory and trophic factor activity including TGF, HGF, LIF, VEGF, EGF, BDNF and NGF, demonstrating that the immunomodulatory properties of the Mesenchymal cell therapy are long-term and actively maintained by continuing cytokine production. We embarked a clinical trial to evaluate of safety and efficacy of mesenchymal cell derived from bone marrow to treat severe respiratory distress in patients with severe COVID – 19 pneumonia.

Cytokine mediated therapy in the treatment of COVID 19 patients

It is a clinical trial to combat the novel COVID 19 for activation of T cells from healthy donors and to develop an enriched cocktail of cytokines, predominantly TH1 type and rich in IFN’s. A cocktail of cytokines when administered to an infected patient, can result in a surge of cytokines in the body of the infected person and will boost his ability to fight the virus. Revamping the altered immune mechanisms due to the viral infection could offer a successful cure with decreased mortality. The project is in Phase 1 stage and approved by Indian Council of Medical Science and Central Drug Standard Control Organisation, Directorate General Health services, Government of India

Convalescent plasma cell therapy

It is an open label, parallel arm, phase I/II clinical trial to evaluate safety and efficacy of convalescent plasma as therapy for Covid-19 Severe SARS- CoV-2 Disease. Convalescent plasma (CP) therapy, a classic adaptive immunotherapy, has been a successful intervention in the treatment of many infectious diseases. CP therapy has shown propitious results in SARS, MERS, and 2009 H1N1 epidemic. CP, obtained from recovered COVID-19 patients who had established a sturdy humoral immunity against the virus, could potentially contain a large pool of neutralizing antibodies against SARS-CoV-2 and eradicating the pathogen from blood circulation and pulmonary tissues. Considering the proven efficacy of CP in past epidemics and we have proposed a clinical trial (IMD/CoV/003/2020) to use CP in patients of COVID 19. Patients who have recovered from SARS-CoV2 and who have been discharged from SARS-CoV2 treatment centres or units could be potential donors for Convalescent Plasma which would be rich in immunoglobulins against SARS CoV2. The project is in Phase 1 stage and approved by Indian Council of Medical Science and Central Drug Standard Control Organisation, Directorate General Health services, Government of India

T-cell activation

T-cell activation is critical for the initiation and regulation of the immune response, activation of T cells which also increases antibody responses. T cells in the human body fight against infection by pathogens and kills mutant cells by specifically recognising them through T cell receptors (TCRs). Based on this basic recognition characteristics cancer immunotherapy has evolved by unleashing the inhibition of immune checkpoints which boosts the antitumor efficacy of genetically engineered T cells.

Currently, we are conducting safety and efficacy trial to evaluate the role of activated T cell therapy in adjuvant settings in patients who have undergone treatment for locally advanced head neck cancer. 3 cycles of ATcT was administered in all these patients as adjuvant therapy after they had completed RT / CTRT. The DFS and OS were 10 months and 35 months. The DFS show that the results appear to similar to the latest immunotherapy trials.

Recombinant viral immunodominant proteins for antibody (IgM/IgG) titration in convalescent patients using ELISA

There are no definite procedures or methods to determine the quantity of viral specific IgM/IgG in the donor convalescent plasma. Therefore, we are proposing to develop simple ELISA based method to determine the IgM/IgG in the donor sera which enables the clinician to take most pragmatic decision for plasma therapy. For this method, we have employed recombinant and most immuno-dominant SARS-CoV2 proteins measure the antibodies elicited in the recovered COVID-19 patients or in convalescent sera.

The novelty in this technique is the designing of the recombinant protein which is immuno-dominant and which can elicit neutralising antibody are considered for this method. The recombinant proteins are expressed in prokaryotic system for the ease of expression and also for expedited production. From NCBI the gene sequence of the S and N structural proteins of the COVID-19 are retrieved. Using the molecular biology techniques genes will be cloned and expressed in prokaryotic expression vectors or systems such as pET22 OR pRSET (Melcher K, 2000). Further using the classical agglutination methods, the reactivity of the recombinant antigens with the sera will be evaluated. Appropriate concentration of the antigens will be employed to run the simple immunoassay to determine the levels of the antibodies against the selected antigens in the convalescent serum before sued in the plasma therapy for COVID-19 patients.