Dataset Information

A Study to Evaluate the Safety and Efficacy of A2B694, a Logic-gated CAR T, in Subjects With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

ABSTRACT: The goal of this study is to test A2B694, an autologous logic-gated Tmod CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), pancreatic cancer (PANC), non-small cell lung cancer (NSCLC), ovarian cancer (OVCA), mesothelioma (MESO), and other solid tumors that express MSLN and have lost HLA-A*02 expression. The main questions this study aims to answer are: Phase 1: What is the recommended dose of A2B694 that is safe for patients Phase 2: Does the recommended dose of A2B694 kill the solid tumor cells and protect the patient’s healthy cells Participants will be required to perform study procedures and assessments, and will also receive the following study treatments: Enrollment and Apheresis in BASECAMP-1 (NCT04981119) Preconditioning Lymphodepletion (PCLD) Regimen A2B694 Tmod CAR T cells at the assigned dose

DISEASE(S): Colorectal Adenocarcinoma,Ovary Cancer,Lung Cancer,Colorectal Cancer,Non Small Cell Lung Cancer,Mesothelioma,Lung Neoplasms,Neoplasms,Ovarian Cancer,Pancreas Cancer,Nsclc,Colon Cancer,Colorectal Neoplasms,Solid Tumor, Adult,Ovarian Neoplasms,Pancreatic Neoplasms,Pancreatic Neoplasm,Rectal Cancer,Non-small Cell Squamous Lung Cancer,Mesom,Crc,Nsclc, Recurrent,Mesothelioma, Malignant,Solid Tumors,Cancer

PROVIDER: 106941 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:This model of the use of chimeric antigen receptor (CAR)-T cell therapy in the treatment of solid tumours is described in the article: "Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept" Odelaisy León-Triana, Antonio Pérez-Martínez, Manuel Ramírez-Orellana and Víctor M. Pérez-García Cancers 2021, 13, 703.; doi: 10.3390/cancers13040703 Comment: This is the first mathematical model, derived from equations 1 and 2, used in the paper. Reproduction of Fig. 5a was achieved by setting alpha_1 = 0.04, different to the value quoted in the article caption for Fig. 5. Abstract: Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial success against B-cell malignancies, which has led to a growing scientific and clinical interest in extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immunosuppressive tumour microenvironment, which is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using the mathematical model, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study computationally, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. We study in silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive production of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. This strategy could benefit from the combination with PD-1 inhibitors and low tumour loads. Our computational results provide theoretical support for the treatment of different types of solid tumours using T cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD-1 drugs after completion of classical cytoreductive treatments.

Project description:This model of the use of chimeric antigen receptor (CAR)-T cell therapy in the treatment of solid tumours is described in the article: "Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept" Odelaisy León-Triana, Antonio Pérez-Martínez, Manuel Ramírez-Orellana and Víctor M. Pérez-García Cancers 2021, 13, 703.; doi: 10.3390/cancers13040703 Comment: This is the second mathematical model, derived from equations 3 to 6, used in the paper. Reproduction of Figure 5b was achieved by setting alpha_1 = 0.183, in substitution for alpha_1 = 0.2 as quoted in the article. Abstract: Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial success against B-cell malignancies, which has led to a growing scientific and clinical interest in extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immunosuppressive tumour microenvironment, which is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using the mathematical model, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study computationally, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. We study in silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive production of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. This strategy could benefit from the combination with PD-1 inhibitors and low tumour loads. Our computational results provide theoretical support for the treatment of different types of solid tumours using T cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD-1 drugs after completion of classical cytoreductive treatments.

Dataset Information

A Study to Evaluate the Safety and Efficacy of A2B694, a Logic-gated CAR T, in Subjects With Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

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