Personalised Cancer Vaccines Using Alphavirus Vectors Seattle Project Corp’s Neoantigen Delivery Platform

Therapeutic cancer vaccines that target tumour-specific neoantigens represent a promising next generation of personalised immunotherapy, particularly for cancers with high mutational burdens such as melanoma and non-small cell lung cancer. A divisional patent from Seattle Project Corp. describes an alphavirus-based vector system for delivering neoantigen expression cassettes – one that addresses both the prediction accuracy problem with existing neoantigen selection methods and the pre-existing immunity problem that hampers delivery using human-derived viral vectors.

The Problem

Personalised cancer vaccines work by identifying somatic mutations unique to a patient’s tumour that generate new peptide sequences (neoantigens) not present in normal tissue. If these neoantigens can be delivered to the patient’s immune system in an immunogenic context, they may stimulate tumour-specific T-cell responses capable of killing the cancer cells.

However, current methods for predicting which tumour mutations will generate therapeutically useful neoantigens have a critical limitation: fewer than 5% of peptides predicted to be presented on tumour cell MHC molecules using gene expression and MHC binding affinity modelling can actually be detected on the tumour cell surface. This low positive predictive value means that most neoantigen vaccines designed using standard prediction pipelines will not deliver actual neoantigens to patients, and the chance of a patient receiving more than one genuine neoantigen in a vaccine is low.

Additionally, standard approaches focus only on cis-acting mutations and miss important sources of neoantigens including mutations in splicing factors that cause aberrant splicing, and mutations that create or remove protease cleavage sites. Standard tumour analysis also risks promoting sequence artefacts or germline polymorphisms as neoantigens, wasting vaccine capacity or risking autoimmunity.

For the vector platform itself, many humans have pre-existing immunity to human viruses from prior natural exposure, which can neutralise recombinant human virus vectors before they can deliver their payload.

What This Invention Does

The patent describes a composition for delivering a neoantigen expression system based on an RNA alphavirus backbone. Alphaviruses such as Sindbis virus and Venezuelan equine encephalitis virus (VEEV) are non-human RNA viruses to which most of the human population has no pre-existing immunity, overcoming the neutralisation problem that affects human virus-derived vectors.

The neoantigen expression system is built around one or more vectors comprising an RNA alphavirus backbone containing a promoter sequence and a polyadenylation signal, combined with a neoantigen cassette. The neoantigen cassette contains tumour-specific, subject-specific MHC class I neoantigen-encoding sequences derived from the patient’s own tumour. Each neoantigen sequence encodes a peptide with at least one alteration from the wild-type sequence, flanked by optional 5′ and 3′ linker sequences. The cassette can optionally include a second promoter, MHC class II antigen sequences, and GPGPG amino acid linker sequences to connect multiple neoantigen elements.

The system is designed to incorporate neoantigens selected using methods that go beyond simple MHC binding affinity prediction, addressing the low positive predictive value problem by identifying neoantigens that are actually presented on tumour cell surfaces.

Key Features

Alphavirus vector backbone. The use of an RNA alphavirus vector avoids the pre-existing immunity problem that neutralises recombinant human viral vectors in many patients, enabling effective delivery even in previously virus-exposed individuals.

Subject-specific neoantigen cassette. The neoantigen sequences are derived from the individual patient’s tumour, making each vaccine a personalised therapeutic tailored to the specific mutational profile of that patient’s cancer.

MHC class I and class II epitopes. The neoantigen cassette can encode both MHC class I epitopes (which activate CD8+ cytotoxic T cells) and MHC class II epitopes (which activate CD4+ helper T cells), enabling a more comprehensive anti-tumour immune response.

GPGPG linker sequences. Neoantigens within the cassette can be linked using GPGPG amino acid sequences, a commonly used strategy to string multiple neoantigen elements together in a polyepitope construct while maintaining independent processing of each element by the proteasome.

Promoter and poly(A) signal. The alphavirus backbone provides the necessary transcriptional control elements to drive neoantigen expression at levels sufficient to stimulate immune responses after delivery.

Who Is Behind It?

The applicant is Seattle Project Corp. of the United States. The named inventors are Blair Wade, Jooss Karin, Rappaport Amy Rachel, Scallan Ciaran Daniel, and Gitlin Leonid. This divisional was filed on 26 February 2026, derived from AU 2023202423, which was itself a divisional of AU 2018266705, which traces to PCT/US2018/031696 (filed 8 May 2018) with US Provisional priority from applications filed in May, June, and November 2017. FB Rice Pty Ltd in Sydney are the Australian patent attorneys.

Why It Matters

Neoantigen-based personalised cancer vaccines have demonstrated proof-of-concept in early clinical studies, with evidence of induced T-cell responses and, in combination with checkpoint inhibitors, tumour regression in some patients. The two technical challenges addressed by this patent – delivery vector immunogenicity and neoantigen prediction accuracy – are the principal obstacles that have limited the clinical effectiveness of early neoantigen vaccine approaches.

By using an alphavirus vector that circumvents pre-existing immunity and by encoding neoantigens selected through methods that identify actually-presented epitopes rather than simply predicted binders, this platform aims to substantially increase the fraction of patients who receive a genuine therapeutic neoantigen in their vaccine. For tumour types such as melanoma, NSCLC, and microsatellite-instable colorectal cancer, which carry high mutational burdens and thus the greatest neoantigen repertoire, this approach could prove particularly impactful.

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AU 2026201462 was published in the Australian Official Journal of Patents on 19 March 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.

Related Concepts

Personalised cancer immunotherapy seeks to harness the patient’s own immune system against tumour-specific targets. Neoantigens – peptides arising from somatic mutations unique to a patient’s tumour – are among the most promising targets because they are absent from healthy tissue. Alphaviruses are non-human RNA viruses that sidestep pre-existing immunity, making them attractive delivery vehicles, while checkpoint inhibitors can amplify the T-cell responses such vaccines stimulate.