Company: CERO
Filing Date: 2025-04-15
Form Type: 10-K
Source: 0001213900-25-032134
Chunk: 105

Company: CERO THERAPEUTICS HOLDINGS, INC.
Filing Date: 2025-04-15
Form: 10-K
Item: Item 1
Chunk 105
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 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.

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