Company: CERO
Filing Date: 2025-01-21
Form Type: S-1/A
Source: 0001213900-25-004742
Chunk: 146

Company: CERO THERAPEUTICS HOLDINGS, INC.
Filing Date: 2025-01-21
Form: S-1/A
Chunk 146
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 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 the brand name Yescarta, and tisagenlecleucel, sold by Novartis under the brand name Kymriah. A third CAR-T cell therapy, brexucabtagene autoleucel, which is comparable to Yescarta and sold by Gilead under the tradename Tecartus, was approved in 2020. Lisocabtagene matraleucel, sold by Bristol Myers Squibb under the brand name Breyanzi, received FDA approval in February 2021 with Bristol Myers Squibb also receiving approval for idecabtagene vicleucel, sold under the tradename Abecma, in March of that year. Most recently, Janssen Biotech received FDA approval for ciltacabtagene autoleucel, brand name