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NCT05877599 trial overview
NCT05877599 Overview Modal
Target Overview
Tumor protein 53 (TP53) is the most commonly mutated gene across all cancer types, with the R175H mutation being the most prevalent TP53 mutation across different solid tumor indications. The T-cell receptor (TCR) utilized in NT-175 recognizes the R175H mutation in the context of HLA-A*02:01, which is the most frequent HLA allele in the US population, present in nearly 50% of individuals.
The NT-175 TCR was identified in tumor infiltrating lymphocytes of a patient with metastatic colorectal carcinoma. Clinical activity of this TCR has been demonstrated in a metastatic breast cancer patient refractory to several lines of hormonal and chemotherapy treatment. The patient received a single dose of autologous T cells engineered to express the TCR and achieved a partial response for 7 months.1
Compound Overview
NT-175 is an autologous T-cell product, expressing a T-cell receptor recognizing mutated TP53 (specifically the R175H mutation in TP53) in the context of HLA-A*02:01. The T-cells are armored through the genetic knock-out of transforming growth factor, beta receptor II (TGFbRII).
NT-175 is an immunotherapy that uses autologous T cells collected from the patient’s blood. Expression of the NT-175 TCR on the patient’s own T cells allows them to recognize and kill tumor cells that express the TP53 R175H mutation and HLA-A*02:01.1 The genetic knock-out of the TGFbRII in NT-175 T-cells abrogates the signaling of the immunosuppressive cytokine TGFβ and enhances anti-tumor efficacy against TGFβ-expressing tumors in vivo.2
Using our proprietary nonviral nuclease-based engineered T-cell manufacturing platform, NT-175 is manufactured at Neogene’s internal manufacturing facility in Santa Monica.
Mechanism of Action
References
NCT05877599 trial overview
NCT05877599 Overview Modal
Abbreviations
HLA
human leukocyte antigen
HNSCC
head and neck squamous cell carcinoma
ITAM
immunoreceptor tyrosine-based activation motif
LCK
lymphocyte-specific protein tyrosine kinase
NSCLC
non-small cell lung cancer
TCR
T-cell receptor
TGFβ
transforming growth factor beta
TGFβRII
transforming growth factor, beta receptor II
TP53
tumor suppressor protein 53
ZAP70
zeta-chain-associated protein kinase 70