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Target Overview
KRAS mutations are among the most prevalent mutations observed in cancers and have been shown to drive tumor development and growth. KRAS G12D is the most prominent mutation in PDAC, with a frequency of approximately 28%. It is also present in approximately 12% of colorectal adenocarcinomas and 4% of NSCLC. Peptides encoding KRAS mutations can be presented by different HLAs. For example, the KRAS G12D variant can be presented by HLA-C*08:02, an HLA type with a frequency of approximately 10% in the Caucasian population in at least one allele.
The NT-112 TCR was originally identified in a 50-year-old colorectal cancer patient (Patient 4095) enrolled in a Phase 2 clinical trial (NCT01174121) at the NCI, which was designed to test whether adoptive transfer of ex vivo expanded tumor-infiltrating lymphocytes (TIL) containing T cells targeting personalized cancer neoepitopes can mediate regression of metastatic solid cancers.1
Compound Overview
NT-112 is an immunotherapy that consists of autologous T-cells derived from a patient's own immune cells that express a T-cell receptor recognizing mutated KRAS G12D in the context of HLA-C*08:02.2 The T-cells are armored through the genetic knock-out of transforming growth factor, beta receptor II (TGFBRII), which abrogates the signaling of the immunosuppressive cytokine TGFβ and enhances anti-tumor efficacy in the tumor microenvironment.
Using our proprietary non-viral nuclease-based engineered T-cell manufacturing platform, NT-112 is manufactured at AstraZeneca’s internal manufacturing facility in Santa Monica.
Mechanism of Action
References
1. Tran E, et al. N Engl J Med. 2016;375(23):2255-226 2. Huang L, Guo Z, Wang F, Fu L. Signal Transduct Target Ther. 2021;6(1):386.
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Abbreviations
HLA
human leukocyte antigen
KRAS
Kirsten rat sarcoma viral oncogene homolog
NCI
National Cancer Institute
NSCLC
non-small cell lung cancer
PDAC
pancreatic ductal adenocarcinoma
TCR
T-cell receptor
CBLB
Cbl proto-oncogene B
CD8αβ
cluster of differentiation 8 alpha beta
TILs
tumor-infiltrating lymphocytes
Target Overview
KRAS mutations are among the most prevalent mutations observed in cancers and have been shown to drive tumor development and growth. KRAS G12D is the most prominent mutation in PDAC, with a frequency of approximately 28%. It is also present in approximately 12% of colorectal adenocarcinomas and 4% of NSCLC. Peptides encoding KRAS mutations can be presented by different HLAs. For example, the KRAS G12D variant can be presented by HLA-C*08:02, an HLA type with a frequency of approximately 10% in the Caucasian population in at least one allele.
The NT-112 TCR was originally identified in a 50-year-old colorectal cancer patient (Patient 4095) enrolled in a Phase 2 clinical trial (NCT01174121) at the NCI, which was designed to test whether adoptive transfer of ex vivo expanded tumor-infiltrating lymphocytes (TIL) containing T cells targeting personalized cancer neoepitopes can mediate regression of metastatic solid cancers.1
Compound Overview
NT-112 is an immunotherapy that consists of autologous T-cells derived from a patient's own immune cells that express a T-cell receptor recognizing mutated KRAS G12D in the context of HLA-C*08:02.2 The T-cells are armored through the genetic knock-out of transforming growth factor, beta receptor II (TGFBRII), which abrogates the signaling of the immunosuppressive cytokine TGFβ and enhances anti-tumor efficacy in the tumor microenvironment.
Using our proprietary non-viral nuclease-based engineered T-cell manufacturing platform, NT-112 is manufactured at AstraZeneca’s internal manufacturing facility in Santa Monica.
Mechanism of Action
References
1. Tran E, et al. N Engl J Med. 2016;375(23):2255-226 2. Huang L, Guo Z, Wang F, Fu L. Signal Transduct Target Ther. 2021;6(1):386.
Clinical trial information
Select trial for more information
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Selected Filter(s)
Abbreviations
HLA
human leukocyte antigen
KRAS
Kirsten rat sarcoma viral oncogene homolog
NCI
National Cancer Institute
NSCLC
non-small cell lung cancer
PDAC
pancreatic ductal adenocarcinoma
TCR
T-cell receptor
CBLB
Cbl proto-oncogene B
CD8αβ
cluster of differentiation 8 alpha beta
TILs
tumor-infiltrating lymphocytes