🇬🇧 Oncolytic immunotherapy against human glioblastoma » Luxembourg Institute of Health
Accueil » Événements » 🇬🇧 Oncolytic immunotherapy against human glioblastoma

Veuillez noter que le contenu n’est disponible qu’en anglais.

🇬🇧 Oncolytic immunotherapy against human glioblastoma

25/04/2024 11:00 Ă  13:30
  • Lecture Series Cancer Research

Speaker

Prof. E. Antonio
Chiocca, MD, PhD

Professor of Neurosurgery, Harvard Medical School Brigham and Women’s Hospital, Neuroscience Center Dana-Faber Cancer Institute, Center for Neuro-Oncology Boston, Massachusetts, USA

Abstract

A “first-in-human” phase 1 trial of intralesional injection of CAN-3110, an immunotherapeutic oncolytic based on herpes simplex virus 1 (HSV1), was conducted in 41 subjects with recurrent high-grade glioma (rHGG). The impact of CAN-3110 on the tumor immune microenvironment was assessed using immunohistochemistry, multiplexed immunofluorescence, TCR-beta DNA sequencing, and bulk RNA sequencing of paired pre- and post-treatment samples. These analyses were combined with patient features to identify potential biomarkers of therapy response in rHGG.

In IDH wild type recurrent glioblastoma (IDHwt rGBM) patients, post-treatment survival times were positively associated with positive pre-treatment HSV1 serology after controlling for additional covariates such as tumor volume, age, gender, CAN-3110 dose, etc. (HR = 0.16, p < 0.001, n = 32, CoxPH). Positive HSV1 serology was also significantly associated with clearance of CAN-3110 from injected tumors. Interestingly, increased intratumoral CD8 and CD4 T cell numbers following treatment were positively associated with prolonged survival in HSV1 seropositive patients (p = 0.017 and 0.026, respectively), but
not when analyses were conducted including HSV1 seronegative patients. Likewise, post-treatment immune expression signatures (such as for antitumor cytokines, T cell traffic, etc.) were more strongly associated with prolonged survival for HSV1 seropositive patients than for seronegative patients, and most assessed immune signatures only became associated with survival after CAN-3110 treatment. Extended survival was also associated with increased TCR-beta diversity following therapy in both the tumor and in PBMCs.

Combined with a lack of observed dose-limiting toxicities and a median post-treatment survival of 14.2 months (95% CI: 9.5-15.7) in IDHwt rGBM patients with positive HSV1 serology, these data provide evidence that intralesional CAN-3110 treatment is capable of generating immune activation in a traditionally immunologically cold tumor in a way that influences survival time—particularly when patients have had prior exposure to HSV1. (clinicaltrials.gov NCT03152318)


Responsible Scientist
Anna
Golebiewska
Simone
Niclou

*Please note that registration is mandatory by sending an email to siu-thinh.ho@lih.lu

LOCATION

CHL – Centre
Room Amphitheatre

4, rue Nicolas Ernest Barblé
L-1210 Luxembourg (Belair)

LECTURE: 11:00am – 12:00pm

MEET & EAT*

12:30pm – 13:30pm

DoCR
Room McClintock (2nd floor)

6A, rue Nicolas-Ernest Barblé
L-1210 Luxembourg

Light lunch provided

Supported by:

Partagez sur

Protection des données

En savoir plus sur la « Notice sur la protection des données : traitement des données personnelles dans le cadre de la gestion des événements  ».

Événements à venir