What is PeptiCRAd

PeptiCRAd

PeptiCRAd (Peptide-coated Conditionally Replicating Adenovirus) is an innovative and unique way of combining two clinically proven cancer immunotherapy approaches: an oncolytic Adenovirus and a peptide vaccine, to take advantage of the best features of both technologies. The idea is straightforward: to use immunogenic viruses as active carriers of tumor-specific peptides to direct the immune system to specifically target and kill cancer cells in 3 distinct ways.

Oncolytic Adenovirus

  • - Tumor-specific replication
  • - Immune-boosting modifications
  • - Tumor-targeting modifications

Tumor-specific Peptides

Poly-lysine

  • - Clinically proven vaccine peptides
  • - Novel tumor peptides
  • - Unique patient-specific neoantigens

Patient-specific Treatment

PeptiCRAd

  • - Multiple different tumor-specific peptides can be adsorbed onto one PeptiCRAd
  • - Multiple tumor-specific antigens can be targeted simultaneously

PeptiCRAd is an oncolytic adenovirus platform, where immunogenic tumor peptides are adsorbed onto the negatively charged viral capsid

Why PeptiCRAd?

Viruses are highly immunogenic, and adenoviruses effectively prime and boost CD8+ T-cell responses in humans (1,2). However, current oncolytic virus-based vaccines primarily induce anti-virus immunity, and the anti-tumor immune response occurs only in a fraction of patients. Peptide vaccines can be highly tumor-targeted, but the low immunogenicity of current approaches limits their clinical utility. By using an oncolytic adenovirus as an active carrier of tumor-specific peptides, we can re-direct the immune response from anti-virus to anti-tumor immunity, and create a robust CD8+ T-cell mediated immune attack against cancer.

The technology is simple: In contrast to oncolytic viral vaccines genetically coding tumor antigens, PeptiCRAd technology is highly adaptive to all cancers. The same carrier virus can be used to treat all cancers and the adaptation occurs simply by coating the virus with different poly-lysine extended peptides – this can be done in 15 minutes. Our unique technology utilizes the remarkable immunogenicity of the adenovirus and simultaneously directs the CD8+ T-cell response toward tumor tissue.

  1. Draper and Heaney (2010). Nat. Rev. Microbial.
  2. Bart et. al. (2014). J. Clin. Invest.

1Immune response against PeptiCRAd-loaded tumor peptides

Following intratumoral PeptiCRAd administration, PeptiCRAd is taken up by antigen presenting cells (APCs). PeptiCRAd triggers activation of APCs via multiple pathogen recognition receptor (PRR) mediated pathways. APCs process peptides and present them on their surface. In the draining lymph node, activated APCs present peptides to naive CD8+ T-cells.

2Immune response against patient-specific unique tumor antigens

PeptiCRAd replication causes tumor cell lysis and the release of tumor associated antigens (TAAs). Danger signals from dying tumor cells activate APCs. APCs take up TAAs and present them. In the draining lymph node, activated APCs present TAAs to naive CD8+ T-cells

3Systemic CD8+ T-cell mediated immune attack against tumors

Local PeptiCRAd treatment initiates a robust systemic CD8+ T-cell immunity against virus-loaded tumor peptides as well as multiple unique patient-specific tumor antigens.

Relevant publications from the IVTLab at the University of Helsinki

Erkko Ylösmäki, Vincenzo Cerullo (2019). Design and application of oncolytic viruses for cancer immunotherapy, Current Opinion in Biotechnology, Volume 65, Pages 25-36, ISSN 0958-1669, https://doi.org/10.1016/j.copbio.2019.11.016. (http://www.sciencedirect.com/science/article/pii/S0958166919301326)

S. Feola, C. Capasso, M. Fusciello, B. Martins, S. Tähtinen, M. Medeot, S. Carpi, F. Frascaro, E. Ylosmäki, K. Peltonen, L. Pastore & V. Cerullo (2018) Oncolytic vaccines increase the response to PD-L1 blockade in immunogenic and poorly immunogenic tumors, OncoImmunology, 7:8, DOI: 10.1080/2162402X.2018.1457596

Erkko Ylösmäki, Cristina Malorzo, Cristian Capasso, Oona Honkasalo, Manlio Fusciello, Beatriz Martins, Leena Ylösmäki, Antti Louna, Sara Feola, Henrik Paavilainen, Karita Peltonen, Veijo Hukkanen, Tapani Viitala, Vincenzo Cerullo (2018). Personalized Cancer Vaccine Platform for Clinically Relevant Oncolytic Enveloped Viruses. Molecular Therapy, Volume 26, Issue 9, Pages 2315-2325, ISSN 1525-0016,https://doi.org/10.1016/j.ymthe.2018.06.008.

Cristian Capasso, Aniket Magarkar, Victor Cervera-Carrascon, Manlio Fusciello, Sara Feola, Martin Muller, Mariangela Garofalo, Lukasz Kuryk, Siri Tähtinen, Lucio Pastore, Alex Bunker & Vincenzo Cerullo (2017) A novel in silico framework to improve MHC-I epitopes and break the tolerance to melanoma, OncoImmunology, 6:9, DOI: 10.1080/2162402X.2017.1319028

Cristian Capasso, Mari Hirvinen, Mariangela Garofalo, Dmitrii Romaniuk, Lukasz Kuryk, Teea Sarvela, Andrea Vitale, Maxim Antopolsky, Aniket Magarkar, Tapani Viitala, Teemu Suutari, Alex Bunker, Marjo Yliperttula, Arto Urtti & Vincenzo Cerullo (2016) Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the antitumor immunity and efficacy against melanoma, OncoImmunology, 5:4, DOI: 10.1080/2162402X.2015.1105429