Right Targets, Right Cells, Right Place

From advancements in gene editing and synthetic biology to first approvals in cell therapies and KRAS-targeted treatments, the cadence of innovation in cancer therapeutics has accelerated over the past decade.

On their own, these new scientific and medical developments have brought treatment options to countless patients suffering from a variety of cancer types. However, for many patients, the potential of these approaches has yet to be fully realized, especially for those patients with advanced solid tumors.

Now is the right time to leverage scientific advancements to deliver potentially curative therapies by unlocking the power of T cells and targeting oncogenic driver mutations.

TCR-T cell therapies: Our in-house, proprietary and differentiated T cell receptor engineered T cell (TCR-T) therapy-enabling platforms () harness state-of-the-art engineering, synthetic biology, and manufacturing technologies to optimize T cell function in the immunosuppressive tumor microenvironment, aiming at sustained clinical responses in patients with solid tumors.

Bispecific T Cell Engagers: Our in-house, proprietary and differentiated bispecific T Cell Engager therapy-enabling platform () harness state-of-the-art affinity maturation capabilities using yeast display modalities to identify specific high affinity TCRs and biotherapeutic technologies to produce T Cell Engager with balanced CD3 binders and extended half-life for optimal T cell engagement, aiming at sustained T cell responses against solid tumors.

Why Oncogenic Drivers

Oncogenic driver mutations, like KRAS, are exclusively expressed in tumor cells and instrumental for the initiation and maintenance of tumor growth. Found in a significant proportion of solid tumor cancers, oncogenic drivers have a varying prevalence depending on the cancer type. KRAS mutations alone are present in 30% of all solid tumors, which makes KRAS the most frequently mutated oncogene in difficult-to-treat solid tumors. These mutations are indispensable during tumor progression, creating a cancer cell dependency on mutated drivers that translates into promising targets for long-term cancer cures. Cell therapies selectively targeting oncogenic driver mutations have the potential to revolutionize cancer treatment by providing more effective and personalized therapies for patients with high unmet medical needs.

Why TCR-T Cell Therapy and bispecific T Cell Engagers

Over the last few years, engineered T cell therapies, like CAR-T cells, have shown tremendous potential in a range of malignant diseases and demonstrated that engineered T cells can induce meaningful and long-lasting clinical responses. However, two of their key limitations are that CAR-T cells require the target antigen to express on the cell surface and that the target antigen is often also expressed on normal cells. Using TCR-T cells opens a new target space by recognizing a broader range of targets, including oncogenic driver mutations, that originate from intracellular proteins inaccessible to CAR-T therapies targeting surface proteins and that are not expressed on normal cells. TCR-T cell therapies with synthetic biology have high specificity and the ability to infiltrate and persist within solid tumors, which enables T cells to thrive in the hostile tumor microenvironment and exhibit improved efficacy against hard-to-treat tumors.

Affini-T’s bispecific T Cell Engagers from the TETHER™ platform are off-the-shelf biologics that redirect and activate the endogenous T cell immune response towards cancer cells expressing specific oncogenic driver targets.

Our Platforms

Autologous TCR-T cell therapies

Our team is pioneering T cell receptor engineered T cell (TCR-T) therapies with cutting-edge, high throughput T cell receptor (TCR) discovery, synthetic biology, manufacturing technologies and gene editing enhancements to target oncogenic driver mutations that strike tumor cells at the core of their biology.

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TAILOR™ Bespoke TCR Discovery for the RIGHT TARGETS

TAILOR™ identifies highly specific and potent TCRs against endogenously presented oncogenic driver peptides using machine learning and high-throughput screening of human T cells. TAILOR™ is a discovery process that enriches for rare T cell populations expressing highly specific and potent TCRs targeting driver mutations. Using machine learning algorithms trained to identify peptide patterns, we detect common motifs of endogenously presented oncogenic driver peptides. Once identified, TCRs are rapidly screened using high throughput functional assays to assess their potency and potential cross-reactivity. Our TAILOR™ platform enables the swift discovery of optimal TCRs for oncogenic driver mutations, accelerating the development of TCR-T cell therapies for solid cancer patients.

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TUNE™ Engineering the RIGHT CELLS to persist in the RIGHT PLACE

TUNE™ provides a diverse array of synthetic biology tools, including switch receptors, cytokine signaling modulators, and co-receptors that enhance the persistence and durability of TCR-T cell therapies. TUNE™ incorporates synthetic biology to enhance the persistence and functional durability of TCR-T cell therapies in the hostile solid tumor microenvironment. These tools include engineered switch receptors that enable T cells to convert negative death signals received in the tumor microenvironment to positive downstream costimulatory signals and survival pathways. Additional receptors include co-receptors that enable CD4 T cells to exhibit a cytotoxic response in addition to boosting CD8 T cell function, and constitutive receptors that provide additional cytokine signals for T cell fitness. Our TUNE™ platform provides a full suite of powerful tools for enhancing the effectiveness of TCR-T cell therapies in hard-to-treat cancers.

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THRIVE™ Manufacturing cell products with phenotypes that THRIVE

THRIVE™ produces T cell therapies utilizing optimized and rapid manufacturing that incorporates gene editing modifications to maximize the therapeutic impact of TCR-T cell therapies. THRIVE™ combines cell therapy manufacturing and gene editing to generate a high yield of fit and proliferative T cells exhibiting naïve and stem cell memory phenotypes. By selecting for stemness and engineering both CD4 T cells and CD8 T cells with our TAILOR™ and TUNE™ platforms, we enhance the potency of TCR-T cells in the presence of tumor-specific antigens and reduce exhaustion in the tumor microenvironment. Novel gene editing systems facilitate advanced cellular engineering including non-viral knock in of TAILOR™ and TUNE™ elements, as well as increased avidity through knock out of the endogenous TCR, which prevents potential mispairing between native and transgenic TCR chains. By modifying cells in a controlled and highly reproducible manner, THRIVE™ aims to improve cellular proliferation, persistence and durability of responses, and ultimately, to eradicate metastatic cells in patients with solid tumors.

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Bispecific T Cell Engagers

Our team is pioneering bispecific T Cell Engager with cutting-edge, high throughput affinity maturation T cell receptor (TCR) discovery and biologics format constructions to target oncogenic driver mutations that strike tumor cells at the core of their biology.

Our Science