ValoTx Approach and Technologies

From our Leaders - ValoTx Technologies Explained

Film is a fantastic way to communicate complex medical science and ideas. We’re delighted therefore to share this film, in which you can hear from our CEO Paul Higham, and our board member Professor Paul Porter, all about how we are reinventing cancer immunotherapy. Our novel immuno-oncology approach teaches T-cells how to become super effective cancer hunting and killing machines.

PeptiCRAd Mechanism of Action - Animated

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.

Immuno-oncology (LEAD)
PeptiCRAd

Oncolytic Adenovirus
(negative charge)

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

Tumor-specific Peptides
(positive charge)

Poly-lysine

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

Patient-specific Treatment
(electrostatic complex)

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

Immuno-oncology (PIPELINE)
PeptiENV

Oncolytic Enveloped Virus
(Vaccinia, HSV)

Tumor-specific peptides
(+ membrane anchor)

Membrane peptide

Patient-specific treatment
(physical complex)

PeptiENV

- PeptiENV has a significantly higher (x10) peptide carrying capacity than PeptiCRAd
- Larger viral genomes that can accommodate more immunomodulatory transgenes
- Potential to enhance the immune responsiveness to existing 3rd party oncolytic virus strategies

Other Platforms
PeptiVAX / PeptiENV / PeptiBAC

Other Platforms

Our other platforms enhance a wide range of existing and novel vaccine platforms with disease specific peptide targets

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.

A selection of publications relevant to understanding technologies associated with Valo Therapeutics and IVTLab.

 

PeptiCRAd first proof-of-concept:

 

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 (2015). 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

 

PeptiCRAd works with heteroclitic peptides:

Capasso C, Magarkar A, Cervera-Carrascon V, Fusciello M, Feola S, Muller M, Garofalo M, Kuryk L, Tähtinen S, Pastore L, Bunker A, Cerullo V.(2017). A novel in silico framework to improve MHC-I epitopes and break the tolerance to melanoma. Oncoimmunology 11;6(9):e1319028. doi: 10.1080/2162402X.2017.1319028

 

PeptiCRAd activity is enhanced in immunosuppressive tumors by the use of ICIs:

Feola S, Capasso C, Fusciello M, Martins B, Tähtinen S, Medeot M, Carpi S, Frascaro F, Ylosmäki E, Peltonen K, Pastore L, Cerullo V. (2018). Oncolytic vaccines increase the response to PD-L1 blockade in immunogenic and poorly immunogenic tumors. Oncoimmunology. 7;7(8):e1457596. doi: 10.1080/2162402X.2018.1457596

 

PeptiCRAd technology is expandable to enveloped viruses - PeptiENV first proof-of-concept:

Ylösmäki E, Malorzo C, Capasso C, Honkasalo O, Fusciello M, Martins B, Ylösmäki L, Louna A, Feola S, Paavilainen H, Peltonen K, Hukkanen V, Viitala T, Cerullo V. (2018). Personalized Cancer Vaccine Platform for Clinically Relevant Oncolytic Enveloped Viruses. Mol Therapy. 5;26(9):2315-2325. Doi: 10.1016/j.ymthe.2018.06.008. Journal cover granted.

 

PeptiCRAd 2.0 - MHC-I and MHC-II peptide coated oncolytic virus:

Tähtinen S, Feola S, Capasso C, Laustio N, Groeneveldt C, Ylösmäki EO, Ylösmäki L, Martins B, Fusciello M, Medeot M, Tagliamonte M, Chiaro J, Hamdan F, Peltonen K, Ranki T, Buonaguro L, Cerullo V (2020). Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy. Cancer Research. 15;80(12):2575-2585. doi: 10.1158/0008-5472.

 

PeptiCRAd ready for clinic:

Erkko Ylösmäki, Leena Ylösmäki, Manlio Fusciello, Beatriz Martins, Petra Ahokas, Hanne Cojoc, Arttu Uoti, Sara Feola, Anna Kreutzman, Tuuli Ranki, Julia Karbach, Tapani Viitala, Petri Priha, Elke Jäger, Sari Pesonen, Vincenzo Cerullo (2021). Characterization of a novel OX40 ligand and CD40 ligand-expressing oncolytic adenovirus used in PeptiCRAd cancer vaccine platform. Mol. Therapy Oncolytics. DOI: https://doi.org/10.1016/j.omto.2021.02.006.

 

PeptiCRAd used with Neoantigens and ERV antigens: 

Peltonen K, Feola S, Umer HM, Chiaro J, Mermelekas G, Ylösmäki E, Pesonen S, Branca RMM, Lehtiö J, Cerullo V (2021). Therapeutic Cancer Vaccination with Immunopeptidomics-Discovered Antigens Confers Protective Antitumor Efficacy. Cancers. 2021; 13(14):3408. https://doi.org/10.3390/cancers13143408

 

PeptiCRAd as a personalised oncolytic cancer vaccine delivering neoantigens:

Feola S, Chiaro J, Martins B, Russo S, Fusciello M, Ylösmäki E, Bonini C, Ruggiero E, Hamdan F, Feodoroff M, Antignani G, Viitala T, Pesonen S, Grönholm M, Branca RMM, Lehtiö J, Cerullo V. (2022). A novel immunopeptidomic-based pipeline for the generation of personalized oncolytic cancer vaccines. Elife 2022 Mar 22;11:e71156. doi: 10.7554/eLife.71156. (IF=8.14).

 

PeptiCRAd as a versatile platform for cancer oncolytic vaccines:

Feola Sara, Russo Salvatore, Martins Beatriz, Lopes Alessandra, Vandermeulen Gaëlle, Fluhler Vinciane, De Giorgi Camilla, Fusciello Manlio, Pesonen Sari, Ylösmäki Erkko, Antignani Gabriella, Chiaro Jacopo, Hamdan Firas, Feodoroff Michaela, Grönholm Mikaela, Cerullo Vincenzo (2022). Peptides-Coated Oncolytic Vaccines for Cancer Personalized Medicine. Frontiers in Immunology, Vol. 13, DOI=10.3389/fimmu.2022.826164