Company: CERO
Filing Date: 2025-02-05
Form Type: S-1/A
Source: 0001213900-25-010230
Chunk: 148

Company: CERO THERAPEUTICS HOLDINGS, INC.
Filing Date: 2025-02-05
Form: S-1/A
Chunk 148
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brane 
 domain anchors the CAR in the lymphocyte’s membrane, bridging the extracellular hinge and antigen recognition domains with the            
 intracellular signaling domain and provides critical stability to the CAR. In addition, the transmembrane domain may also interact with   
 other transmembrane proteins that enhance CAR function.                                                                                   |

| ● | Intracellular                                                                                                                                
 signaling domain. The other end of the CAR, inside the T cell, is connected to two or more contiguous domains responsible for activating     
 the lymphocyte when the CAR binds to its target antigen. The first, found in almost all CAR constructs, is called CD3ξ. The CD3ξ             
 domain delivers an essential primary signal within the T cell and is the natural basis for activation of these lymphocytes. The current      
 generation of CAR-T configurations generally employ one or more costimulatory domains, such as CD28, to provide enhanced activation signals  
 and augment lymphocyte activity. Together, these signals result in the proliferation of the CAR-enabled T cells and selective cellular       
 destruction. In addition, activated CAR-T cells stimulate the local secretion of cytokines and other molecules that can recruit and activate 
 additional immune cells to increase target elimination.                                                                                      |

The assembly of these core CAR components is depicted in the schematic presented below to which certain non-coding regulatory sequences may be used to augment viral gene expression. Delivery of conventional CAR-T cell therapies involves a single viral vector. 88 Conventional CAR-T cell therapies often utilize a lentiviral vector for the delivery of CAR specific genes. Lentiviral particles offer a well-characterized transduction mechanism and are recognized as efficient and convenient vehicles for gene transfer as they demonstrate broad tropism, or activity, in a wide array of cell types, and can be used to target quiescent, or non-dividing, cells. In addition, they do not integrate close to the promoter regions of genes with the frequency of other gene delivery alternatives and lack the immunogenicity of DNA-based vectors, characteristics which provide for enhanced safety. The use of a lentiviral vector to facilitate ex vivo clinical gene transfer has been demonstrated to be safe in humans for two decades with minimal genotoxicity observed in hundreds of patients following gene transfer into T cells or hematopoietic progenitor cells. Currently, six CAR-T cell therapies have been approved by the FDA for the treatment of certain types of hematological cancers. The first two, approved in 2017, are axicabtagene ciloleucel, sold by Gilead Sciences under