Company: CERO
Filing Date: 2025-04-15
Form Type: 10-K
Source: 0001213900-25-032134
Chunk: 107

Company: CERO THERAPEUTICS HOLDINGS, INC.
Filing Date: 2025-04-15
Form: 10-K
Item: Item 1
Chunk 107
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 underscored by the prevalence
of solid tumor malignances. The American Cancer Society estimates that solid tumor cancers accounted for more than 1.7 million of the
1.9 million people newly diagnosed with cancer in 2021. Even in hematological malignancies with approved CAR-T cell therapies, less toxic
orthogonal treatment approaches are needed as cure rates for CD19-targeted CAR-T cell therapies do not exceed 60%.

Challenges to the use of
cellular therapy to address solid tumors often relate to difficulty in developing receptors directed towards targets expressed in high
frequency on cancer cells as well as overcoming the immunosuppressive microenvironments that contribute to ineffective immune responses.
The tumor stroma, made up of a dense fibrotic matrix, often surrounds solid tumors and acts as a physical barrier, which restricts CAR-T
cell access to the tumor. CAR-T cell activity may be further hindered by the tumor microenvironment (“TME”). In the TME, multiple
cell types which drive immunosuppression infiltrate solid tumors, including myeloid-derived suppressor cells, tumor-associated macrophages,
and regulatory T cells. The interaction of these cells and the tumor cells increases the expression of signaling molecules that enable
tumor cell proliferation while dampening the generation of co-stimulatory signals necessary for T cell expansion and persistence. In addition,
TME-associated immune dysfunction may result in a down regulation of MHC class I molecules, limiting proper antigen presentation and T
cell proliferation. Collectively, these attributes of solid tumors enable them to avoid normal immune surveillance. Increased engagement
of the endogenous host response is an important, if not critical, component of CAR-T cell therapy clinical success as the recruitment
into the tumor of bystander lymphocytes has been observed in tumor biopsies from patients with curative CAR-T cell therapy. Enhancing
the host’s own response to tumor cells offers an important opportunity to improve current CAR T cell responses.

CAR-T recipients may also
incur serious adverse events (“SAEs”), perhaps the most prominent of which is cytokine release syndrome (“CRS”).
Believed to be related to the rapid proliferation and activation of T cells upon detection of a target antigen, severe or life-threatening
CRS was noted in a significant number of patients who participated in the registrational trials of FDA-approved CAR-T therapies. These
SAEs can result in patients requiring longer hospitalizations and more intensive medical care. The frequency and severity of observed
SAEs is one of the primary