A fully individualized cell therapy platform
Targeting solid cancer with a novel T cell receptor (TCR) therapy approach.
Engineered T cell therapies have demonstrated great benefit to patients with some difficult-to-treat cancers, bringing new hope to address the current limitations of treatments available today. While these therapies have transformed the treatment paradigm for some patients with blood cancers, a large unmet need remains for patients with advanced solid tumors – driven in part by a lack of safe and broadly expressed target antigens. Neogene aims to overcome these limitations by identifying T cell receptor genes targeting patient-specific tumor mutations for use in fully individualized engineered T cell therapies.
Using tumor mutation profiles to engineer fully individualized T cell therapies.
The development and evolution of cancer is driven by the accumulation of DNA mutations in cancerous cells. Some of the DNA mutations that arise in cancer cells can generate antigens with an altered amino acid sequence, which are known as neoantigens. Given their exclusive occurrence in the tumor, neoantigens represent safe targets for cancer therapy. Importantly, neoantigens can render the tumor ‘visible’ to T cells of the immune system and T cells that target neoantigens have been identified in patients experiencing regression of advanced metastatic tumors.
The spectrum of neoantigens expressed by tumors differs between patients, even for those suffering from tumors of the same histological origin. Neogene’s proprietary neoantigen TCR discovery and T cell engineering platform aims to identify neoantigens – and suitable TCRs to target them – for each individual patient and to enable the engineering of T cells with these neoantigen specific TCRs for patients suffering from a broad spectrum of solid tumors.
Targeting multiple neoantigens to enhance efficacy and durability of Neogene’s engineered TCR therapies.
Solid tumors frequently express multiple neoantigens. Neogene’s scientific approach aims to exploit this common occurrence by utilizing a set of TCRs to target several different neoantigens in each treated patient. The goal of this strategy is to reduce the possibility for the development of therapy-induced resistance mechanisms and increase the strength and duration of the therapeutic response.
Neogene aims to engineer a multi-specificity T cell therapy containing more than one TCR to simultaneously target different neoantigens and limit tumor escape while enhancing overall efficacy.
Neogene’s proprietary neoantigen TCR discovery and T cell engineering platform delivers an industry-leading approach to realizing engineered T cell therapies targeting tumor neo-antigens for patients with solid tumors.
Tumor material is highly enriched for neoantigen TCRs compared to peripheral blood. Our platform allows for the isolation of TCR genes specific for tumor neoantigens identified in patient tumor material obtained from routine treatment biopsies.
The tumor biopsy of each individual patient is utilized to genetically analyze the tumor cells and the T cells contained within the tumor. Our proprietary neoantigen TCR discovery and T cell engineering platform uses state-of-the-art DNA sequencing, DNA synthesis and genetic screening tools to identify the neoantigens of the patient’s tumor as well as TCR genes specific for these neoantigens within the tumor biopsies with high sensitivity and specificity. These TCR genes form the basis for a fully individualized T cell therapy of the patient’s cancer.
A scalable manufacturing process and novel genetic engineering approaches will be utilized to introduce the identified TCR genes into the patient’s own blood T cells, which are thereby equipped to recognize tumor neoantigens. The goal of leveraging multiple TCR genes against different tumor neoantigens is to ensure a fully individualized and potentially multi-specificity T cell response against the tumor.
Leveraging cutting-edge synthetic biology tools to identify neoantigen-specific TCR genes from routine biopsies, we perform a two-pronged in-depth genetic profiling on the tumor sample:
- First, we uncover the tumor mutations that lead to neoantigens
- Second, we capture the TCR sequence repertoire of tumor infiltrating T cells.
This synthetic biology-based approach replaces the need for viable patient T cells during the TCR isolation process and offers potentially major advantages with respect to standardization, scalability, speed and cost, which are critical to achieve our goal of bringing fully individualized engineered T cell therapies to patients. An additional advantage of this approach includes the ability to access TCRs derived from different subtypes of neoantigen specific T cell (CD8+ and CD4+ T cells) that are enriched within tumors compared to peripheral blood.
We have validated our TCR identification and selection platform in a variety of tumors, including hard-to-treat cancers. This reinforces the pan-cancer potential of this technology which we continue to optimize and evolve. We’re heavily investing in novel synthetic biology and T cell engineering tools to continue to improve our engineered T cell therapies.
We are developing a therapeutic pipeline of T cell therapies with pan-tumor potential, starting with fully individualized TCR therapies, while continuing to invest in next-generation technologies to enhance and optimize the impact of these transformational therapies for patients.
Presentations and Publications