The partners have received a VLAIO grant to drive innovation in neoantigen identification and validation for personalized T-cell immunotherapy

The ImmunoPepX research project from myNEO Therapeutics and Janssen Pharmaceutica in collaboration with KU Leuven, VITO, and VUBhas been awarded a government grant by Minister Crevits and the VLAIO (Agency for Innovation and Entrepreneurship) of € 1.48 million. This project validates neoantigens predicted to be successful for personalized immunotherapy, based on extensive characterization of antigens in colorectal cancer patients. The partners aim to subsequently extrapolate this approach to other tumor types.

Neoantigens are patient-specific, abnormal proteins found on the surface of cancer cells that are recognized by the immune system. Immunotherapy attempts to activate and target the immune system against these neoantigens so that  cancer cells are attacked and killed. Correctly identifying neoantigens for each individual patient is a crucial element in enabling targeted personalized therapy.

Although prediction of neoantigens is essential for a successful therapy, contemporary predictive models yield suboptimal results due to a lack of data as well as experimental validation. Central to the ImmunoPepX project is therefore improved high-throughput and high-confidence neoantigen identification. The project establishes a modular platform to accurately identify and characterize neoantigens in colorectal cancer (CRC), with the potential to extend the approach to other tumor types.

This new platform is based on a complementary strategy in which neoantigens are identified by means of a vastly improved computational pipeline, a cutting-edge immune-peptidomics approach and a high throughput methodology for determining the neoantigen specificity and reactivity of T-cells.

Development of a “best-in-class” neoantigen identification platform
There remains a lot of room for improvement in current predictive models in terms of sensitivity and specificity. In addition, no high throughput protocols are currently available for the validation of neoantigens which complicates the implementation of effective immunotherapies.

Within the project, a unique integrated dataset will be collected using all partners’ expertise, which will bring together clinically relevant information for 15 CRC patients. This includes a complete screening of the DNA, RNA, and immunopeptidome of the tumor tissue (via whole genome sequencing, transcriptome sequencing, and mass spectrometry, respectively), combined with single cell TCR sequencing and immunogenicity assays. This extensive allows identification and validation of neoantigens in these patients with considerably improved accuracy, and drives improvements in the predictive models for future use.

“A tumor neoantigen identification platform powered by gold standard validation processes, is invaluable in our mission to make personalized immunotherapy more accessible”,  says Cedric Bogaert, CEO of myNEO Therapeutics. “The ImmunoPepX project results in an unparalleled comprehensive best-in-class neoantigen platform integrating all the necessary elements for prediction of immunogenic neoantigens.”

Personalized T-cell therapy for cancer patients
The neoantigen discovery platform will be applied to a set of samples from 15 CRC patients. This indication was chosen because of the expertise of both VUB and KU Leuven and because the majority of CRC patients does not respond to current forms of immunotherapy with checkpoint inhibitors. This group of CRC patients is characterized by cold tumors with low mutation levels (low TMB, MSS).

“The success of T-cell or checkpoint-based therapies in melanoma have not translated uniformly to cold tumors. Ligandome studies of MSS CRC patients suggest that mutated exonic antigens are rare in these tumors with low TMB, indicating that a general approach to neoantigen identification will need to expand beyond mutated antigens alone.” – Prof. dr. Sabine Tejpar, KU Leuven

Within the project, the aim is to evaluate the resulting list of useful neoantigens for further use in the development of tumor suppressing antigen (TSA) vaccines or adaptive T-cell therapies (ACT). In addition to the optimization of the neoantigen prediction platform, the project also focuses on tools that facilitate T-cell repertoire profiling (cell-sorting strategies, sequencing platforms, and computational methods). These enable the identification of tumor reactive T-cells in tumor and lymph node samples.

“The development of efficient tools that allow us to unravel the immune components of difficult-to-treat cancers will be invaluable for the development of new, innovative therapies.” – Joke Reumers, Head Discovery Omics – Janssen Pharmaceutica

About the partners
Janssen Pharmaceutica, one of the Pharmaceutical Companies of Johnson & Johnson, is an integrated R&D expertise center worldwide for the development of new medicines within four disease areas: disorders of the central nervous system, oncology, immunology, and infectious diseases/vaccines.

myNEO Therapeutics (Ghent) is a biotech company that pursues development and validation of neoantigen-driven cancer immunotherapies. Its platform allows to rapidly identify for each patient the neoantigen target repertoire based on patient biopsy and blood, used to improve upon the current set-of therapy options.

Janssen Pharmaceutica and myNEO Therapeutics are collaborating in this project with 3 research groups:

• KULeuven, the Molecular Digestive Oncology group (Prof. Sabine Tejpar), examines the identity of colorectal tumors with a specific focus or molecular tumor patterns associated with specific tumor types, disease mechanisms, and tumor heterogeneity. This group will be responsible for patient inclusion, collection, and processing of patient samples and data interpretation.
• VITO (Geert Baggerman and Kurt Boonen), the Flemish Institute for Technological Research, has expertise in proteomics with a strong focus on oncology. The VITO will provide improved neoantigen detection using optimized immune-peptidomics assays.
• VUB, Laboratory for Molecular and Cellular Therapy (Prof. Karine Breckpot, Prof. Kris Thielemans) focuses on the development of innovative immunotherapeutic and immunomodulatory strategies, including the optimization of DC-based vaccination as well as methods to modulate the tumor environment. The LMCT lab will assist Janssen with immunogenicity profiling.