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Programmable T Cells

ArsenalBio deploys a synthetic biology toolkit to genetically program a patient’s own T cells to potentially eradicate solid tumors.

To address the multi-faceted problem of cancer, we believe that cell therapies must undergo a fundamental re-writing of the innate programming of T cells to install therapeutic actions that would not normally occur in nature.

Developing these next-generation products takes a highly coordinated effort spanning immunology, synthetic biology, automation and computation.

We combine these disciplines to program our T cells with multiple synthetic biology modules that work together to potentially:

  • Enable faster T cell growth
  • Prevent activity in healthy cells
  • Increase and extend potency of anti-tumor activity
  • Deliver additional anti-cancer functions to the tumor
  • Improve targeting and specificity to tumor cells
  • Prevent tumor immune evasion

CITE Engineering and Manufacturing

All of our synthetic biology modules are engineered into T cells via a single genetic modification in Chromosome 11 using a highly specific CRISPR-based approach called CITE (CRISPR Integration of Transgene via Electroporation).

CITE minimizes the risk of insertional mutagenesis inherent to viral engineering methods and maximizes the potential payload that can be inserted into the T cell genome.

CITE: Non-Viral Cell Programming via a single genomic insertion site

ArsenalBio CITE: Multi-functional DNA cassette inserted at single safe-harbor site.
Other approach: Multiple integrations/cuts (e.g. random viral integrations + knockouts)

Our CITE-enabled clinical manufacturing uses electroporation-mediated delivery of our therapeutic program, encoded in DNA, into the T cell genome. Insertion of this program as a single piece of DNA at a specific genomic site aims for improved product homogeneity and consistency relative to random integration approaches such as lentiviral or transposon delivery.

Our manufacturing process generates a high frequency of memory phenotype T cells, with an absence of CAR on the cell surface to delay T cell exhaustion and prevent any therapeutic activity until cells reach the tumor. The process is also optimized to minimize collection-to-release timing, and enable treatment of a patient in less time than conventional viral processes.

Autologous manufacturing enabled by CITE programming

1. Patient apheresed. 2: Transport to ArsenalBio manufacturing. 3: T cell isolation. 4: T cell activation. 5: image demonstrating CITE site-specific integration. 6: T cell expansion. 7: Cryo-preservation. 8: Lot release testing. 9: Transport to clinic. 10: Patient infused.

To learn more about our cell therapy development programs, visit our Pipeline page.

Synthetic modules

ArsenalBio is engineering enhanced CAR T cell therapies by creating new synthetic modules and incorporating them into T cells to program them to execute new behaviors, much in the same way that smartphones get new features as new versions are released.

Our synthetic modules are combined and inserted together into a specific site in the T cell genome. With each product developed, we are including additional modules with the goal to deliver greater anti-tumor benefit to patients through improved potency, evasion of the suppressive tumor microenvironment, and delayed T cell exhaustion:

Each Product in pipeline is built upon a growing cell therapy feature set

AB-1015 Ovarian Cancer. GS94 Insertion- Homogeneity: Precise edit. Logic gate - Specificity and potency. shRNA v1 - potency and TME resistance
AB2100 Kidney Cancer. GS94 Insertion - Homogeneity precise edit. Logic gate - specificity and potency. shRNA v2 TME resistance++. SPA - Potency: less exhaustion

Solid tumor targeting specificity: Dual antigen logic gate requires two targets to activate T cell killing

healthy cell types and cancer cells

Logic Gating

The first thing a T cell must do is recognize a tumor and discriminate cancer tissues from healthy tissues. At ArsenalBio we are solving this with logic gating.

We engineer our T cells to have a logic gate with two sensors that only activate together at the tumor site. Only the tumor site has both signals to trigger both sensors and release the full killing potential of the T cell. Since healthy cells don’t have both of these signals, they are protected from the cell killing effect of the T cell.

Careful choice of the signals, which are proteins on the surface of cells at the tumor site, allows the T cell to be programmed with the right sensors to hunt and kill tumor cells while sparing healthy tissues.

This logic gate approach to T cell activation has the potential to create more precisely targeted cell therapies that can treat more tumor types to help more patients.

A Powerful Platform

We are building a powerful end-to-end cell engineering platform that utilizes rational product design and rapid, iterative optimization for accelerated and scalable discovery of best-in-class therapeutic candidates.

Our comprehensive library screening assays and data-driven approaches leverage computational biology and machine learning capabilities that enable our scientists to examine more fully the universe of possible therapeutic constructs, rather than exploring a handful product candidates based more heavily on intuition. This high-throughput data influences experimental design, which generates even more data that is used to iteratively build better systems for creating optimal medicines.

Our platform-powered product development includes:

Synthetic circuit designs: Massive, functionally diverse design space accessible through DNA synthesis and assembly
Integrated screening platform: Deep molecular and phenotypic screening in vitro and in vivo
Lead compositions: Tailored to disease targets and biology

By leveraging these various technologies, we can build an arsenal of adaptable medicines to eradicate cancer.