CARTemis-1 / Andalusian Public Foundation for Health Research Management of Seville - LARVOL DELTA

New Optimized Academic Anti-BCMA CAR (CARTemis-1): How Does the Manufacturing Process Impact CAR-T Cell Features? (ASH 2023) - "ConclusionsCARTemis-1 has been rationally designed to increase anti-tumor efficacy and overcomes sBCMA inhibition. To our knowledge, this is the first study analyzing the impact of the manufacturing process in the dynamics of the CAR-T immunophenotype highlighting the importance of the immunophenotypic characterization of CAR-T cells throughout the manufacturing process to define the optimal cell culture protocol and expansion time to increase CAR-T cell product fitness."

CAR T-Cell Therapy • IO biomarker • Graft versus Host Disease • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • EGFR • IL15 • IL2 • IL7 • LAG3 • PD-1

Validation of GMP Lentiviral Vector Production for CAR T-Cell Therapy in the Spanish Public Health System: Development of New QC Required By Aemps (Spanish FDA) (ASH 2024) - "Thus, GMP LV production at ViPro-IBIS represents a robust platform within the Spanish public health system for CAR T-cell therapy clinical trials, allowing to provide LV in a more rapid and affordable way for the trials approved by the AEMPS in the region/country (including ours : SPCD19M-CAR for lymphoma and CARTemis-1 (BCMA CAR) for myeloma). Our platform may serve as a model for improvement for CAR T-cell treatments for the patients."

CAR T-Cell Therapy • Viral vector • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

Assessing CAR-T Cell Product Quality: The Crucial Role of Metabolic and Persistence Analysis after Antigen Stimulation (ASH 2024) - "Methods BCMA-CAR T lymphocytes were generated with 4-1BB (CARTemis-1-BB) and CD28 (CARTemis-1-28) costimulatory domains...Conclusions Flow cytometry and cytotoxicity analyses performed before and after a single antigen stimulation do not demonstrate significant differences between two different CAR-T cell products. By contrast, the determination of persistence in repeated antigen stimulation assays and the metabolic analysis following one antigen stimulation clearly showed significant functional differences which might allow to select the most optimized CAR-T cell product for clinical therapy."

CAR T-Cell Therapy • IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • IL15 • IL7 • TGFB1

Next-generation BCMA-targeted chimeric antigen receptor CARTemis-1: the impact of manufacturing procedure on CAR T-cell features. (PubMed, Cell Oncol (Dordr)) - "CARTemis-1 has been rationally designed to increase antitumor efficacy, overcome sBCMA inhibition, and incorporate the expression of a safety-gene. The generation of CARTemis-1 was successfully validated under GMP standards. A phase I/II clinical trial for patients with multiple myeloma will be conducted (EuCT number 2022-503063-15-00)."

CAR T-Cell Therapy • IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • IL15 • IL2 • IL7

UNDERSTANDING THE ROLE OF CAR-NEGATIVE CELLS IN THE EFFICACY AND SAFETY OF CAR-T THERAPIES (EHA 2024) - "Our research aims to investigate how the CAR-negative population affectsthe functionality and safety of the CARTemis-1 product, an anti-BCMA CAR...Correlation studies between cell number in Tisagenlecleucel products and toxicity in patients (n=25)revealed a significantly higher total infused T cell count/kg in patients experiencing ICANs (p=0... During CAR production, the CAR-negative population exhibits increased expansion resulting in decreasedtransduction rates over time. Despite higher activation and exhaustion observed in CAR-positive cells, purifiedCAR-positive cells displayed similar anti-tumor cytotoxicity with decreased toxicity, suggesting the possibility ofusing lower purified cell doses without sacrificing effectiveness."

Clinical • IO biomarker • Oncology • CD69 • IL15 • IL2 • IL2RA • IL6 • IL7 • ISG20 • LAG3 • PD-1

OPTIMIZING THE ACADEMIC ANTI-BCMA CAR CARTEMIS-1: ASSESSING THE IMPACT OF MANUFACTURING PROCEDURE ON CAR-T CELL FEATURES (EHA 2024) - "CARTemis-1 introduces two main optimizations: enhanced target recognition resultingin heightened anti-tumor effectiveness and resistance to sBCMA inhibition. As far as we know, this is the firstresearch highlighting the importance of immunophenotypic profiling of CAR-T cells across manufacturingprocedure to define the best cell culture protocol and expansion time to increase product fitness."

CAR T-Cell Therapy • IO biomarker • Graft versus Host Disease • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • IL15 • IL2 • IL7 • LAG3 • PD-1

CARTemis-1: Trial of an Investigational Drug After Rejecting the Relapse of an Allogeneic Transplant (clinicaltrials.gov) - P1/2 | N=25 | Not yet recruiting | Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla | Trial completion date: Jan 2028 ➔ Dec 2029 | Initiation date: Jan 2024 ➔ Dec 2024 | Trial primary completion date: Jan 2028 ➔ Dec 2029

IO biomarker • Trial completion date • Trial initiation date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Automated Lentiviral Vectors Production For CAR-T Cell Therapy at HUVR-IBiS (EBMT-EHA 2024) - "Our refined manual production of lentiviral vectors (LVs) allows us to successfully obtain in 6-8 weeks the LVs needed to treat a patient with HSP-CAR19M or Cartemis-1 (BCMA-CAR)... In conclusion, the semi-automated LVs production is successful, being the best strategy the use of iCELLis Nano bioreactor (PEI, single harvest) plus the use of ÄKTA Flux/Pure system for filtration and concentration. This allows the obtention of high functional titer LVs in less time (10 days for 8 patients) for the CAR-T therapy of our patients."

CAR T-Cell Therapy • Viral vector • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

How Does the Manufacturing Procedure Impact CAR-T Cell Features? (EBMT-EHA 2024) - "CARTemis-1 optimizations include improved target recognition with increased anti-tumor efficacy, and no susceptibility to sBCMA inhibition. To our knowledge, this is the first study highlighting the importance of immunophenotyping CAR-T cells throughout the manufacturing process to define the optimal cell culture protocol and expansion time to increase product fitness."

CAR T-Cell Therapy • Graft versus Host Disease • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Transplantation • IL15 • IL7 • LAG3 • PD-1

CAR- Population: Impact on Functionality and Safety of CAR-T Products (EBMT-EHA 2024) - "Our study focuses on the effects of the CAR- population on CARTemis-1 product (anti-BCMA CAR) functionality and safety...Correlation studies in patients infused with Tisagenlecleucel products and toxicity (n=24) were performed and a significantly higher total infused T cell count/kg was seen in patients experiencing ICANs (p=0.053) (Figure 1E)... CAR- population shows enhanced expansion, leading to reduced transduction percentages. Purified CAR+ demonstrated greater cytotoxicity with lower toxicity, suggesting possible reduction in cell doses without compromising efficacy."

Clinical • Oncology • IL15 • IL2 • IL6 • IL7

CARTemis-1: Trial of an Investigational Drug After Rejecting the Relapse of an Allogeneic Transplant (clinicaltrials.gov) - P1/2 | N=25 | Not yet recruiting | Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla | Initiation date: Sep 2023 ➔ Jan 2024

IO biomarker • Trial initiation date • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation