High-precision analysis and manufacturingTechnologies
Annoca has developed, validated and deployed a proprietary technology platform based on libraries of highly engineered human cells that enables high-precision and standardized analysis of T-cell biology. Our technology platform rapidly identifies and validates new disease antigens, in addition to identification, characterization and engineering of TCRs in an industrialised process. Anocca’s own manufacturing facility enables integration of technology-driven analyses into manufacturing control and multiple independent TCR-modified T-cell therapy (TCR-T) clinical programs.
The T-cell biology challenge
T-cells are the front line of the adaptive immune system. They are responsible for detecting new threats in the body and orchestrating an appropriate immune response. The fundamentals of how T-cells operate inside the body have been established for decades; however, the immense complexity of T-cell immunity has limited the development of therapies that precisely harness or manipulate T-cell responses. Unlocking the immense potential of T-cell biology for treatment of a wide range of diseases requires a high-precision, systematic and industrialised approach to the analysis of T-cell immunity.
Harnessing a diverse and complex natural defense system
T-cells are a type of white blood cell and part of the adaptive immune system responsible for discriminating between molecules produced by our own normal tissues, from those that come from foreign entities like viruses, or from dysfunctional cells of tumours. T-cells detect ‘antigens’ that represent molecules processed within the cells of our body, and displayed at the cell surface for sampling by T-cells. T-cells are able to specifically detect the massive number of possible antigens because each new T-cell is equipped with an essentially unique T-cell receptor (TCR). TCRs that detect specific antigens displayed on the surface of target cells provide signal to the T-cell that triggers an immune response against the detected antigen target.
Most cells in our body process antigens and display them on the cell surface for T-cells to sample. A family of proteins called Human Leukocyte Antigens (HLA) display antigens at the cell surface. Unique TCRs are created each time a new T-cell is produced, which allows T-cells to recognise the massive amount of potential HLA-displayed antigens.
Each individual carries dozens of highly diverse HLA genes and the precise combination of genes is unique to each individual. This means that the immune system of one individual is capable of presenting antigens to T-cells in a range of different contexts. This range is unique to each individual, whilst allowing some degree of sharing with common HLA gene variants.
Inter- and intra- individual diversity is an important aspect of our immune defences against rapidly changing pathogens like viruses, ensuring that our immune system can detect new antigens. However, this diversity makes it challenging to determine which antigens are presented in what version of the HLA proteins at the cell surface, and also means that the analysis should effectively be repeated for each individual.
The production of many millions of new T-cells occurs each day within each individual and their TCRs are intricately selected against the HLA-antigen repertoire of that individual. This makes finding TCRs that are suitable for targeting antigens for an individual a challenging process, requiring many steps of selection, validation and characterisation to ensure safety and efficacy of those TCRs when deployed in a therapeutic context.
Anocca has developed unique technologies that harness this complex and intricate natural defence system and is deploying these in the development of next-generation T-cell therapies.
Leveraging the adaptive immune system for therapeutic use requires precise information about specific HLA-displayed antigens and TCRs that target those antigens.
Anocca’s platform uses engineered human cells to precisely mimic how cells display antigens in each individual patient, and how T-cells bearing specific TCRs respond to those antigens. Anocca is able to rapidly assemble customised toolkits comprising living human cells that recapitulates targeted HLA-antigen-TCR interactions for each individual patient, or group of patients. Our toolkit can be deployed in a variety of ways to identify, characterise and even engineer disease antigens and the TCRs that target those antigens. This is made possible by a range of proprietary genetic and molecular technologies that are built-in to Anocca’s engineered cells.
Rapidly identifying and validating new disease antigens
Anocca solves the complexity challenge by constructing large libraries of proprietary engineered antigen presenting cells (eAPCs), where each cell carries a single HLA gene, presenting a single HLA protein at the cell surface. Along with a number of other engineered eAPC fetures, Anocca can precisely map and characterise the antigens presented by the HLA repertoire of each individual in a genuine cellular context. The platform allows Anocca to discover novel disease antigens that can be targeted both to segments of patient populations, and to targeting specific disease anitgens on an entirely individualised basis.
Discovery and engineering T-cell Receptors to treat disease
Anocca has created a range of proprietary genetic and cellular tools to identify, characterise and engineer TCRs in an industrialised process. This is based on sophisticated automated TCR gene sequencing coupled to a genetic toolbox to rapidly synthesise TCR genes in the laboratory. Screening and characterisation of identified and synthesised TCRs is conducted using different forms of engineered TCR-presenting cells (eTPC) to carefully select and optimise therapeutic TCR candidates. Optimised and validated TCRs form the basis of novel cellular therapies to treat disease.
A differentiated approach
Anocca has developed a powerful technology platform designed to address the analytical bottleneck in fully exploiting the current revolution in targeted immunotherapies that directly harness, or indirectly manipulate, the T-cell immune system. Anocca’s approach is to leverage functional cell biology readouts that both reduce analytical complexity and establish highly systematic workflows and is the first industrialised platform for T-cell immunity analysis that is standardised, automatable and scalable across all aspects of the T-cell therapy pipeline in addition to other modalities that target T-cell immunity.
High-precision T-cell biology
Anocca’s approach to the high-precision analysis of T-cell biology deploys a range of cell biology, molecular genetics and molecular biology tools that recapitulate targeted aspects of T-cell immunity in the laboratory. Using this approach Anocca is able to directly analyse the authentic T-cell biology with extreme precision and efficiency without relying on computational predictions, synthetic approximations or non-human animal models.
Industrialised T-cell biology
At the heart of Anocca’s innovative platform is the standardised and efficient production of genetic constructs and programmable engineered human cells that can be customised to recapitulate targeted aspects of T-cell immunity of each individual patient, or group of patients that share genetic and disease attributes. The industrialised and reproducible production of these customisable toolkits enables a range of analytical platforms that precisely analyse T-cell biology with the scale, precision and efficiency required to unlock the therapeutic potential of T-cell immunity.
Anocca operates a unique 5 000 m² in-house clinical scale manufacturing and process development facility.
Manufacturing capabilities include production of viral vectors for the genetic modification of patient T-cells, and incorporates all processes from receipt of patient cells, to cryopreservation and distribution of the final cell therapy product. Quality control laboratories within the manufacturing facility deploy unique assay systems based on our proprietary technologies.