Local delivery of accutox® synergises with immune-checkpoint inhibitors at disrupting tumor growth

Sep 21, 2026

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The Accum® platform was originally designed to concentrate biomedicines in target cells by promoting endosomal-to-cytosol escape, yet unconjugated Accum® was found to induce death across multiple cancer cell lines, including resistant lines. The study develops and characterizes AccuTOX® via flow-cytometry, cell assays, ROS and endosomal break readouts, antigen presentation studies, and RNA-seq in EL4 T-cell lymphoma. Intratumoral AccuTOX® is assessed alone or combined with immune-checkpoint inhibitors in murine solid tumor models.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Graphical Abstract

Background

Bikorimana et al. Journal of Translational Medicine (2024) 22:532 [https://doi.org/10.1186/s12967-024-05340-2](https://doi.org/10.1186/s12967-024-05340-2) Journal of Translational Medicine RESEARCH Open Access Local delivery of accutox® synergises with immune-checkpoint inhibitors at disrupting tumor growth Jean Pierre Bikorimana1†, Nehme El‑Hachem2,3†, Jamilah Abusarah4, Marina Pereira Gonçalves5, Roudy Farah1, Gabrielle A. Mandl 1, Sebastien Talbot6, Simon Beaudoin7, Daniela Stanga7, Sebastien Plouffe7 and Moutih Rafei 1,4,5* Abstract Background The Accum® platform was initially designed to accumulate biomedicines in target cells by inducing endosomal‑to‑cytosol escape. Interestingly however, the use of unconjugated Accum® was observed to trigger cell death in a variety of cancer cell lines; a property further exploited in the development of Accum®‑based anti‑cancer therapies. Despite the impressive pro‑killing abilities of the parent molecule, some cancer cell lines exhibited resist‑ ance. This prompted us to test additional Accum® variants, which led to the identification of the AccuTOX® molecule. Methods A series offlow‑cytometry and cell‑based assays were used to assess the pro‑killing properties of AccuTOX® along with its ability to trigger the production of reactive oxygen species (ROS), endosomal breaks and antigen presentation. RNA‑seq was also conducted to pinpoint the most prominent processes modulated by AccuTOX® treatment in EL4 T‑cell lymphoma. Finally, the therapeutic potency of intratumorally‑injected AccuTOX® was evaluated in three different murine solid tumor models (EL4, E0771 and B16) both as a monotherapy or in combi‑ nation with three immune‑checkpoint inhibitors (ICI) . Results In total, 7 Accum® variants were screened for their ability to induce complete cell death in 3 murine (EL4, B16 and E0771) and 3 human (MBA‑MD‑468, A549, and H460) cancer cell lines of different origins. The selected compound (hereafter refereed to as AccuTOX®) displayed an improved killing efficiency (~ 5.5 fold compared to the parental Accum®), while retaining its ability to trigger immunogenic cell death, ROS production, and endosomal breaks. Moreover, transcriptomic analysis revealed that low dose AccuTOX® enhances H2‑Kb cell surface expression as well as antigen presentation in cancer cells. The net outcome culminates in impaired T‑cell lymphoma, breast cancer and melanoma growth in vivo especially when combined with anti‑CD47, anti‑CTLA‑4 or anti‑PD‑1 depending on the animal model. Conclusions AccuTOX® exhibits enhanced cancer killing properties, retains all the innate characteristics displayed by the parental Accum® molecule, and synergizes with various ICI in controlling tumor growth. These observations will certainly pave the path to continue the clinical development of this lead compound against multiple solid tumor indications. †Jean Pierre Bikorimana and Nehme El‑Hachem have contributed equally to the study. *Correspondence: Moutih Rafei [moutih.rafei.1@umontreal.ca](moutih.rafei.1@umontreal.ca) Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http:

FAQs

What is AccuTOX® in this study, and why was it developed?

AccuTOX® is identified as an Accum® variant developed after observing cell death induction by unconjugated Accum® and noting resistance in some cancer cell lines. The work tests Accum® variants to improve anti-cancer activity.

How was AccuTOX® evaluated experimentally?

The study used flow-cytometry and cell-based assays to assess pro-killing effects, reactive oxygen species (ROS) production, endosomal breaks, and antigen presentation. RNA-seq was also performed to identify key processes modulated in EL4 T-cell lymphoma.

What were the main findings about tumor killing and immune effects?

AccuTOX® improved killing efficiency (about 5.5-fold versus parental Accum®) while retaining immunogenic cell death features, including ROS production and endosomal breaks. Low-dose treatment enhanced H2-Kb surface expression and antigen presentation, leading to impaired lymphoma, breast cancer, and melanoma growth, especially with specific immune-checkpoint inhibitors.

Sep 21, 2026

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