Company: CERO
Filing Date: 2025-02-07
Form Type: 424B3
Source: 0001213900-25-011071
Chunk: 158

Company: CERO THERAPEUTICS HOLDINGS, INC.
Filing Date: 2025-02-07
Form: 424B3
Chunk 158
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 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.

<div align='center'>88</div>

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 201