Periodic Reporting for period 1 - CD20CARNAPT (iTANK: a nuniversal technology to boost the efficacy of CAR T cell therapies by inducing dual mode-of-actio)
Période du rapport: 2022-10-01 au 2023-09-30
Chimeric antigen receptor CAR-T cell therapy has been approved as a second/third-line treatment for patients with chemotherapy-resistant B cell tumors. So far, four therapies with CD19 CAR-T cells have been approved in the EU for B-cell leukemia and lymphoma (Yescarta, Kymriah, Tecartus, and Breyanzi). However, there are 40-50% of patients who will relapse or are refractory to treatment. Many challenges such as antigen loss/heterogeneity, local immunosuppression, and CAR-T cell exhaustion hamper CAR-T cells' efficacy against B cell tumors. These hurdles also hampered the treatment efficacy drastically for other solid tumors.
Elicera developed a new technology platform called iTANK (ImmunoTherapies Activated with NAP for efficient Killing) to enhance the efficacy of all CAR-T cell therapies by inducing a dual mechanism-of-action in the treatment of lymphomas and other solid tumours. The iTANK platform arms CAR-T cells with a transgene encoding a strong immune activator, namely the Neutrophil-Activating Protein (NAP) from Helicobacter pylori. NAP is released only when CAR-T-cells bind to tumour cells, and the locally released NAP can induce a so-called bystander immune activation thus overcoming key challenges for CAR-T therapy.
Previous studies demonstrated superior efficacy of iTANK CAR-T cell therapy in various tumor models, without elevated toxicity.
In this project, Elicera aims to 1) establish a GMP process for the iTANK CAR-T cells manufacturing, and 2) conduct First-in-Human clinical trial to assess the safety, efficacy, and the mode-of-action for iTANK-armed CAR-T cells.
Success of this project will have significant impact of the CAR-T cell therapy fields: 1) improve the overall efficacy of CAR-T therapy against lymphoma; 2) demonstrating the mode-of-action and safety for the iTANK technology; 3) provide a new platform for enhancing other CAR-T cell therapy efficacy as the iTANK technology is compatible with other CAR-T therapies. 4) Provide a blueprint for the platform and will deliver knowledge and experience that can accelerate other projects currently in the pre-clinical phase.
Elicera developed a new technology platform called iTANK (ImmunoTherapies Activated with NAP for efficient Killing) to enhance the efficacy of all CAR-T cell therapies by inducing a dual mechanism-of-action in the treatment of lymphomas and other solid tumours. The iTANK platform arms CAR-T cells with a transgene encoding a strong immune activator, namely the Neutrophil-Activating Protein (NAP) from Helicobacter pylori. NAP is released only when CAR-T-cells bind to tumour cells, and the locally released NAP can induce a so-called bystander immune activation thus overcoming key challenges for CAR-T therapy.
Previous studies demonstrated superior efficacy of iTANK CAR-T cell therapy in various tumor models, without elevated toxicity.
In this project, Elicera aims to 1) establish a GMP process for the iTANK CAR-T cells manufacturing, and 2) conduct First-in-Human clinical trial to assess the safety, efficacy, and the mode-of-action for iTANK-armed CAR-T cells.
Success of this project will have significant impact of the CAR-T cell therapy fields: 1) improve the overall efficacy of CAR-T therapy against lymphoma; 2) demonstrating the mode-of-action and safety for the iTANK technology; 3) provide a new platform for enhancing other CAR-T cell therapy efficacy as the iTANK technology is compatible with other CAR-T therapies. 4) Provide a blueprint for the platform and will deliver knowledge and experience that can accelerate other projects currently in the pre-clinical phase.
The main achievements are as follows:
1. Established a fully-automated process for CAR20(NAP)-T manufacturing. We have optimized the starting material, cell transduction protocol, cell expansion protocol. The final engineered drug product meets the release criteria.
2. Implemented the manufacturing process in GMP lab.
3. Finalize whole process from patient blood collection to final infusion. We demonstrated vein-to-vein time of 17 days, which is significantly shortened compared to current commercially available CAR-T cells that have a median vein-to-vein time of 54 days.
4. Established all QC release assays for CAR20(NAP)-T drug product. Release assay
5. Established all assays for analyzing patient sample for demonstrating the iTANK mode-of-action.
6. Submission of Clinical Trial Application to Swedish Medical Products Agency (MPA) and application to Ethics Committee (EC). Approval received from EC and conditional approval received from MPA. Condition is that we validate the GMP-production process and this work is ongoing.
1. Established a fully-automated process for CAR20(NAP)-T manufacturing. We have optimized the starting material, cell transduction protocol, cell expansion protocol. The final engineered drug product meets the release criteria.
2. Implemented the manufacturing process in GMP lab.
3. Finalize whole process from patient blood collection to final infusion. We demonstrated vein-to-vein time of 17 days, which is significantly shortened compared to current commercially available CAR-T cells that have a median vein-to-vein time of 54 days.
4. Established all QC release assays for CAR20(NAP)-T drug product. Release assay
5. Established all assays for analyzing patient sample for demonstrating the iTANK mode-of-action.
6. Submission of Clinical Trial Application to Swedish Medical Products Agency (MPA) and application to Ethics Committee (EC). Approval received from EC and conditional approval received from MPA. Condition is that we validate the GMP-production process and this work is ongoing.
1) Success on this project will provide proof-on-concept for iTANK technology. We then aim to further develop iTANK-armed CAR-T cell therapies for other indications. Initial work has already started. Elicera has pre-clinically developed CAR-T cells targeting IL13Ra2 for glioblastoma therapy. Initial data demonstrated its efficacy and no off-targets during screening against most human cell surface and secretome proteins.
2) Success on this project will provide the field with new iTANK technology, which can be used for enhancing other CAR-T cell therapies.
3) Success on this project will provide the market with a new drug for B-cell malignancy treatment, with enhanced therapeutic efficacy.
4) Success on this project will strengthen Elicera’s intellectual property protection on iTANK technology.
2) Success on this project will provide the field with new iTANK technology, which can be used for enhancing other CAR-T cell therapies.
3) Success on this project will provide the market with a new drug for B-cell malignancy treatment, with enhanced therapeutic efficacy.
4) Success on this project will strengthen Elicera’s intellectual property protection on iTANK technology.