The text discusses a novel therapeutic approach for treating
solid tumors driven by the
KRAS oncogene. The KRAS G12V mutation, which is prevalent but lacks targeted treatments, is addressed by a T cell therapy called AFNT-211. This therapy utilizes engineered T cells that express a specific T cell receptor (TCR) for the KRAS G12V mutation. The engineered cells are equipped with a CD8α/β coreceptor to facilitate a coordinated immune response and a FAS-41BB switch receptor that converts a death signal from the
tumor into a costimulatory signal, thereby enhancing T cell persistence and response.
The efficacy of
AFNT-211 was evaluated both in vitro against various KRAS G12V-expressing cancer cell lines and in vivo using mouse models with human tumor grafts. Safety studies were conducted to examine potential cross-reactivity and alloreactivity, and the manufacturing process involves expanding autologous T cells using a lentiviral transduction method that maintains stem-like qualities.
Results showed that AFNT-211 induced substantial cytokine release, T cell expansion, and tumor cell death when cocultured with tumor cell lines. The incorporation of the CD8α/β coreceptor allowed for
CD4+ T cell recognition of the KRAS G12V mutation, enhancing cytotoxicity. The FAS-41BB receptor significantly increased the strength and duration of the anti-tumor response, particularly against tumor cells expressing
FASL. No significant cross-reactivities or alloreactivities were detected. In vivo studies in mice demonstrated a strong anti-tumor effect.
The manufacturing platform for AFNT-211 is capable of producing a large quantity of
TCR-engineered T cells with high naive and central memory T cell frequencies and minimal exhaustion markers. The preclinical findings indicate that AFNT-211 has a potent and safe profile, making it a promising candidate for clinical trials in patients with
advanced or metastatic solid tumors who possess the HLA-A*11:01 allele and a KRAS G12V mutation.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
