SNAP Application: Personalized Cancer Vaccine
Avidea’s Personalized Cancer Vaccine (PCV)
Avidea’s PCV consists of peptide neoantigens linked to polymeric-TLR-7/8 agonists that are chemically programmed to self-assemble into nanoparticles.
The Personalized Cancer Vaccine Treatment Paradigm
Personalized Cancer Vaccines aim to expand T cells that target the unique mutational signature present in each individual’s tumor. The vaccine is designed and manufactured specifically for each patient at the time of diagnosis.
Avidea’s Proprietary Innovations in Personalized Cancer Vaccines
Avidea’s Personalized Cancer Vaccine (PCV) utilizes the SNAP platform, ensuring that peptide neoantigens and immunostimulants are packaged into uniformly-sized and loaded nanoparticles irrespective of the neoantigen composition. This unprecedented formulation control enables efficient delivery to and uptake by antigen-presenting cells that promote anti-tumor T cell immunity.
Avidea’s PCV is designed to offer improved neoantigen identification, manufacturing, formulation, breadth of immunogenicity, and T cell quality, which collectively maximize therapeutic efficacy.
Avidea’s PCV enables refinements of the neoantigen prediction algorithm
A major challenge facing conventional peptide-based PCVs is that peptides have highly variable physical and chemical properties based on their unique sequences, which leads to formulation heterogeneity and unpredictable pharmacokinetics upon administration.
The SNAP platform ensures that all peptide neoantigens are formulated into nanoparticles of a uniform size (~20 nm diameter), irrespective of the neoantigen sequence. This formulation consistency means that the biological data that trains crucial aspects of the neoantigen prediction algorithm are not confounded by formulation heterogeneity or unpredictable pharmacokinetics.
Using data sets generated with Avidea’s PCV, Avidea has identified the parameters that lead to superior neoantigen prediction.
manufacturing of patient-specific antigens
Avidea’s proprietary tags allow for rapid, automated manufacturing
Similar to other PCV approaches, Avidea manufactures patient-specific peptide neoantigens by automated solid-phase peptide synthesis.
However, an innovation introduced by Avidea is the use of a tag sequence onto the peptide neoantigen during manufacturing.
Avidea’s proprietary tag sequence technology:
Standardizes peptide properties
Enables the synthesis of “difficult” (hydrophobic) peptides
Enables automated purification, thereby overcoming a major manufacturing bottleneck
Collectively, these innovations reduce manufacturing costs and shorten needle-to-needle time.
Formulation of patient-specific antigens
The SNAP platform is a chemically-defined composition and allows for unprecedented material loading
Traditional particle-based vaccine technologies rely on an empirical formulation process to combine peptide antigens, immunostimulants, and inert carriers. These approaches yield formulations that have significant variability introduced by the unique properties of each peptide neoantigen.
With the SNAP platform, Avidea’s PCV is chemically-defined: every antigen – regardless of the peptide sequence – is incorporated into particles at the same rate, and there is no variability across batches.
Additionally, the SNAP platform enables a degree of mass loading that is unprecedented. Whereas traditional particle formulations often contain less than 1% of peptide antigen by mass of particle (>99% inert carrier), each SNAP particle consists of ~50% peptide by mass.
The unprecedented antigen loading enabled by the SNAP platform ensures that high peptide concentrations are released in the endosome of antigen-presenting cells for highly efficient peptide presentation to T cells.
induction of tumor-specific T cell responses through IMMunization
Avidea’s PCV leads to significant improvement in the efficiency for inducing cytotoxic T cell responses
Avidea’s PCV includes the following design features that enable efficient priming of neoantigen-specific T cell immunity:
Optimal particle size for promoting uptake by antigen-presenting cells (dendritic cells)
Co-delivery of an adjuvant (TLR-7/8 agonist) rationally selected to promote cytotoxic T cell immunity
Enzyme-degradable linkers that enable efficient release of the neoantigen from the particle to enable T cell priming
In preclinical models, the SNAP platform induces CD8 T cell responses to 50% of predicted neoantigens, a greater than 5-fold improvement over conventional formulations.
This higher efficiency for inducing T cell responses may lead to improved cancer therapies, especially for patients with cancers with low tumor mutational burdens, such as breast, prostate, and colorectal cancers, where there are fewer neoantigens available to target.
Enable T cells to eliminate neoplastic cells
Intravenous administration of Avidea’s PCV – a unique capability of the SNAP platform – leads to enhanced T cell quality and more effective tumor clearance
Avidea’s PCV is designed to enable vaccination by any route of administration and for use in combination with myriad complementary immunotherapies. Intravenous administration of Avidea’s PCV induces T cells that are of higher phenotypic and functional quality than T cells induced by peripheral (e.g., subcutaneous, intramuscular, intradermal) administration.
As most other vaccine technologies are not suitable for administration by the intravenous route, Avidea’s PCV is uniquely positioned to offer optimal magnitude, breadth, and quality of T cell responses needed to maximize therapeutic efficacy.
Confounded prediction algorithm
Slow and costly manufacturing
Empirical, laborious formulation
Exhausted T cells
Accurate prediction algorithm
Rapid, high-throughput manufacturing
Chemically-defined, user-friendly formulation
Efficient T cell induction
Potent T cell effector functions