ASCO 2023: Unleashing Precision: AFNT-211 Targets KRAS G12V Mutations in Solid Tumours with Potent Efficacy

ASCO 2023: Unleashing Precision: AFNT-211 Targets KRAS G12V Mutations in Solid Tumours with Potent Efficacy


KRAS mutations are commonly found in various solid tumours and play a significant role in cancer development and progression. While targeted therapies exist for KRAS G12C mutations, there is a lack of treatments for the more prevalent KRAS G12V mutations. Clinical trials have shown promise with TCR-T cell therapies, but their effectiveness is limited by the suppressive nature of the tumour microenvironment (TME). AFNT-211 is an autologous T cell therapy that has been genetically modified to express an HLA-A*11:01 KRAS G12V-specific TCR. It is also engineered with the CD8α/β co-receptor and a FAS-41BB switch receptor to enhance T cell persistence and achieve long-lasting clinical responses.

When AFNT-211 was cultured with various tumour cell lines expressing KRAS G12V, it exhibited significant secretion of effector cytokines, T cell proliferation, and efficient killing of tumour cells. The presence of the CD8α/β co-receptor facilitated recognition of KRAS G12V by CD4+ T cells, leading to improved overall cytotoxicity. The incorporation of the FAS-41BB switch receptor amplified both the strength and durability of the anti-tumor response, especially against tumour cells expressing FASL. Extensive testing, including XScan mutagenesis and off-target peptide analysis, demonstrated no significant cross-reactivity. Additionally, no alloreactivity was observed against a panel of lymphoblastoid cell lines representing the most common HLA types in the US population.

In an in vivo mouse xenograft model, AFNT-211 exhibited a potent anti-tumor response. The Thrive manufacturing platform used by Affini-T consistently produces a high quantity of TCR-engineered T cells, ranging from >30-40e9, with a significant proportion of these cells displaying characteristics of naïve and central memory T cells while expressing minimal exhaustion markers.

In summary, AFNT-211, an autologous T cell therapy engineered to target KRAS G12V mutations, shows promising results in terms of cytokine secretion, T cell proliferation, and tumour cell killing. The inclusion of the CD8α/β co-receptor and the FAS-41BB switch receptor enhances the therapy’s efficacy and durability. Thorough testing ensures minimal side effects and cross-reactivities. The therapy’s potent anti-tumor response in preclinical models highlights its potential as a targeted treatment for patients with KRAS G12V-mutated tumours.

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