PeptiCHIP is a novel microchip-based solution that enables rapid, accurate, user-friendly and standardized tumor neoantigen identification from small tumor biopsies. By addressing the technological limitations that are a major hurdle for the clinical translation of cancer immunotherapies, it will offer more meaningful and cost-effective neoantigen identification for immunotherapy companies, clinicians and researchers. The technology is particularly valuable for those looking to validate antigens that can be used for the clinical development of dendritic cell-based therapies, T-cell receptor designs, monoclonal antibody creation, or as the coating of oncolytic viruses. The PeptiCHIP platform is currently in the commercialisation phase that will lay the foundation for a high-potential spin-off company.
Clinical translation of cancer immunotherapies remains elusive since many patients fail to respond to current approaches. To overcome this challenge, immunotherapies must be engineered to target the specific vulnerabilities of each patient’s tumor. This greater degree of personalization can be achieved using neoantigens that direct the patient’s immune system to recognize the tumors, invoking a strong and highly specific anti-tumor response. Unlike tumor-associated antigens (TAAs), neoantigens are not encoded by the human genome and are therefore not displayed by major histocompatibility complexes (MHC) on healthy cells.
Personalized cancer immunotherapies that depend on the accurate identification of tumor neoantigens include autologous dendritic cell-based vaccines, neoantigen-specific antibodies, and neoantigen-coated oncolytic viral vectors. However, currently available neoantigen identification methods have significant limitations: they are time-consuming (weeks to months), laborious, expensive and inaccurate, as they rely on the prediction of MHC-mediated peptide presentation. Alternative direct chromatography-based detection techniques are available, but their requirement for tumor material far exceeds the quantities obtained in tissue biopsies, preventing clinical neoantigen analysis altogether. Moreover, very few laboratories are sufficiently equipped to identify neoantigens, which impedes research and development of novel neoantigen-based immunotherapies.
Unlocking the full potential of cancer immunotherapies therefore requires more accurate, sample-conserving and cost-effective methods to identify immunogenic neoantigens that will permit effective targeting to the patient's tumor.
Together with the HEX software algorithm for selection of the most promising neoantigens, PeptiCHIP has the potential to overcome the hurdles in the clinical translation of personalized cancer immunotherapies due to its innovative technical features:
- Accuracy: precise identification of tumor neoantigen signatures is an absolute prerequisite for development of effective personalized immunotherapies. PeptiCHIP purification enables direct determination of neoantigen signatures, unlike the sequencing-based or other microarray chip-based technologies, which merely predict the peptide signature expressed on the tumor cell’s surface.
- Speed: processes tumor material at an unparalleled rate – within 1 hour – compared with at least 48 hours for competing technologies.
- Low sample requirement: no sample is lost in the closed system, in contrast to standard methods that involve a substantial loss of valuable tumor material due to multiple ultracentrifugation and chromatography steps. Since the requirement for tumor material is much lower compared to current state-of-the-art, PeptiCHIP is compatible with current clinical tumor biopsy practices.
- Cost-saving: the running cost for PeptiCHIP-based analyses is significantly lower than that of the less accurate and cumbersome state-of-the-art.
- Convenience: PeptiCHIP is easy to integrate into existing analysis workflows. It is quick and easy to use and does not require additional training or specialized biochemical personnel.
The main inventors of PeptiCHIP are Prof. Vincenzo Cerullo and Dr. Sara Feola. Ph.D. student Jacopo Chiaro contributed to the development of the HEX software. Scientific collaborators that were pivotal for the development of PeptiCHIP, HEX and the associated procotols include Ass. Prof. Tiina Sikanen and her Chemical Microsystems Laboratory at Faculty of Pharmacy, University of Helsinki, and Prof. Janne Lehtiö's research group at Karolinska Institutet.
PeptiCHIP was developed as part of the ERC Consolidator project PEPTICRAD (2016-2021), ERC Proof-of-Concept project PeptiCHIP (2019-2021) and Business Finland Research-to-Business project PeptiCHIP (2018-2021). IPR is owned by the University of Helsinki and managed by Helsinki Innovation Services Ltd.
PeptiCHIP: Feola et al. PeptiCHIP: A Microfluidic Platform for Tumor Antigen Landscape Identification. ACS Nano, 15, 10, 15992-16010, available Open Access at: https://pubs.acs.org/doi/10.1021/acsnano.1c04371 (October 2021)
HEX: Chiaro et al. Viral Molecular Mimicry Influences the Antitumor Immune Response in Murine and Human Melanoma, Cancer Immunology Research 2021;9:981–93, available Open Access at: https://cancerimmunolres.aacrjournals.org/content/9/8/981 (August 2021)
HEX video: https://fb.watch/7kB69haMvt/ (interview with Jacopo Chiaro)
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