A biologic-device combination product delivering tumor-derived antigens elicits immunogenic cell death-associated immune responses against glioblastoma.

Authors

• Christopher Cultrara
• Christopher Uhl
• Kenneth Kirby
• Essam Abed Elrazaq
• Amelia Zellander
• David W Andrews
• Charles B Scott
• Lorenzo Galluzzi
• Mark A Exley
• Jenny Zilberberg

Publication/Presentation Date

8-1-2023

Abstract

BACKGROUND: IGV-001 is a personalized, autologous cancer cell-based immunotherapy conceived to deliver a tumor-derived antigenic payload in the context of immunostimulatory signals to patients with glioblastoma (GBM). IGV-001 consists of patient-derived GBM cells treated with an antisense oligodeoxynucleotide against insulin-like growth factor 1 receptor (IGF1R) and placed in proprietary biodiffusion chambers (BDCs). The BDCs are then exposed to 5-6 Gy radiation and implanted at abdominal sites for ~48 hours. IGV-001 has previously been shown to be generally safe with promising clinical activity in newly diagnosed GBM patients.

METHODS: Mouse (

RESULTS: IGV-001 causes oxidative and endoplasmic reticulum stress in GL261 cells, resulting in a cytotoxic response that enables the release of antigenic material and immunostimulatory, ICD-associated molecules including ATP and HMGB1 from BDCs. Immunophenotyping confirmed that IGV-001 increases the percentage of dendritic cells, as well as effector, and effector memory T cells in BDC-draining lymph nodes. Consistent with these observations, preventative IGV-001 limited tumor progression and extended overall survival in mice intracranially challenged with GL261 cells, a benefit that was associated with an increase in tumor-specific T cells with effector features. Similar findings were obtained in the Hepa 1-6 model. Moreover, therapeutically administered IGV-001 combined with PD-1 delayed progression in GBM-bearing mice.

CONCLUSIONS: These results support treatment with IGV-001 to induce clinically relevant ICD-driven anticancer immune responses in patients with GBM.

Volume

11

Issue

8

ISSN

2051-1426

Published In/Presented At

Cultrara, C., Uhl, C., Kirby, K., Abed Elrazaq, E., Zellander, A., Andrews, D. W., Scott, C. B., Galluzzi, L., Exley, M. A., & Zilberberg, J. (2023). A biologic-device combination product delivering tumor-derived antigens elicits immunogenic cell death-associated immune responses against glioblastoma. Journal for immunotherapy of cancer, 11(8), e006880. https://doi.org/10.1136/jitc-2023-006880

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

37550054

Department(s)

Administration and Leadership

Document Type

Article