Release Tx Announces iScience Publication on Encapsulated Cell Technology for Sustained, Localised Anti-CTLA-4 Cancer Immunotherapy
Peer-reviewed preclinical study in a colorectal cancer model demonstrates antitumour activity and immune modulation within the tumour despite substantially lower systemic antibody exposure than systemic ipilimumab, with lower systemic exposure associated with fewer observable signs of treatment-related toxicity.
Release Therapeutics (Release Tx) is pleased to announce the publication of a new peer-reviewed preclinical study in iScience, a Cell Press journal, evaluating the use of its encapsulated cell technology (ECT) for sustained, local delivery of a human anti-CTLA-4 antibody in cancer immunotherapy.[1]
The study, entitled “Encapsulated Cell Therapy for Local Anti-CTLA-4 Delivery in Cancer Immunotherapy,” was conducted by researchers from Release Tx, Geneva University Hospitals (HUG) and the University of Geneva (UNIGE). In a mouse model of colorectal cancer, it evaluated the feasibility and efficacy of peritumoural implantation of the Myo-P3®, a living implant combining an immortalised human myoblast (IHM) cell line engineered to continuously secrete low doses of a human anti-CTLA-4 antibody with the Myo-Pod®, a miniaturised, cylindrical hollow fibre macroencapsulation device for cell housing and implantation.
The study builds on the MVX-ONCO programme undertaken when the Company operated as MaxiVAX SA. Within this programme, MVX-ONCO-1 combined autologous, inactivated tumour cells with an encapsulation system providing sustained, local release of the immune adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) and progressed to a first-in-human Phase I study in patients with advanced, treatment-refractory solid tumours. The development of MVX-ONCO-1 was recognised in 2026 with the prestigious Pfizer Research Prize in Oncology, awarded to researchers at HUG and UNIGE, which hold an exclusive licence to MVX-ONCO, including the anti-CTLA-4-secreting cell line and associated ECT.[2]
With the transition to Release Tx in 2023, the Company shifted its development focus to severe disorders of the central nervous system (CNS), applying the underlying technology to a different set of therapeutic delivery challenges while continuing to support the advancement of its earlier oncology work with HUG and UNIGE. The new publication in iScience adds to the broader evidence base supporting ECT as a therapeutic delivery platform, which already includes clinical experience in oncology, and further strengthens the scientific foundation of the technology now being advanced by Release Tx in CNS disorders.
Engineering Sustained Local CTLA-4 Blockade
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is an immune checkpoint receptor expressed on activated T cells and regulatory T cells (Tregs) that acts as a natural brake on immune activity. This inhibitory effect occurs when CTLA-4 binds to molecules on the body’s antigen-presenting cells, limiting the signals that would otherwise activate T cells.[3] The antigen-presenting cells also display antigens to T cells, providing information about the presence of foreign or abnormal cells and helping determine whether an immune response should be mounted.
In the presence of a tumour, the same inhibitory pathway can limit the activation of T cells that recognise tumour antigens, including cytotoxic CD8+ T cells that can directly kill cancer cells. This has made CTLA-4 an important target for cancer immunotherapy, as blocking the receptor can help release this immune brake and strengthen T-cell responses against the tumour. However, systemic CTLA-4 blockade can also disrupt normal immune regulation throughout the body, leading to potentially significant immune-related toxicities.[4]
In the study, IHMs were engineered to continuously secrete low doses of a human IgG1 monoclonal antibody targeting CTLA-4 and were encapsulated within the Myo-Pod, a miniaturised cylindrical hollow fibre capsule with a semi-permeable membrane. The loaded capsule was then implanted peritumorally in a human CTLA-4 knock-in mouse model of colorectal cancer, enabling sustained local secretion of the anti-CTLA-4 antibody in the vicinity of the tumour. The Myo-Pod has been shown to allow selective bidirectional molecular exchange between the capsule and implantation site, enabling outward diffusion of therapeutic proteins and inward diffusion of oxygen and nutrients to support the viability of the encapsulated cells, while the membrane immuno-isolates them from the host immune system.[5]
The core in vivo evaluation comprised two studies. In an initial feasibility and efficacy study, mice implanted peritumorally with a single Myo-P3 were compared with mice receiving systemic intraperitoneal injections of ipilimumab, a clinically approved human IgG1 anti-CTLA-4 monoclonal antibody, as well as mice receiving a Myo-Pod containing unmodified IHMs (Myo-PWT) and untreated controls.
A second, longer-term dose-escalation study then evaluated four adjoined Myo-P3 capsules implanted around the tumour. The same comparator groups were included, alongside one additional group receiving a single peritumoural injection of ipilimumab, allowing the researchers to compare sustained antibody delivery from the encapsulated cells with both systemic and locally injected anti-CTLA-4 therapy.
Sustained Local Delivery with Antitumour Activity and Reduced Systemic Exposur
In the initial study, mice implanted with a single Myo-P3 and those treated with systemic ipilimumab, administered by intraperitoneal injection at 10 mg/kg twice weekly for two weeks, exhibited a statistically significant delay in tumour progression compared with untreated controls. Tumour growth was monitored for up to 72 days after treatment initiation, with individual mice sacrificed earlier if tumour volume grew to exceed 1,000 mm3 or for ethical reasons. The Myo-PWT control group also exhibited a tendency towards slower tumour progression, although this did not reach statistical significance in pairwise comparisons with each of the other treatment groups. The researchers hypothesised that the presence of unmodified IHMs may itself have influenced the local tumour environment, potentially through competition for nutrients or a non-specific immune response to the human cells, although this was not established in the study.
Notably, Myo-P3- and ipilimumab-treated mice experienced a significant survival benefit compared with untreated controls, with 2 of 8 Myo-P3-treated mice and 8 of 10 ipilimumab-treated mice exhibiting complete regression of the established tumour. No statistically significant difference in survival was observed between the active treatment groups, while two mice in the systemic ipilimumab group died a few days after injection, which the researchers considered likely to be related to injection toxicity. The six Myo-P3-treated mice that did not achieve complete tumour regression were euthanised during follow-up after reaching the study’s tumour-burden endpoint. Myo-P3 treatment also showed a trend towards improved survival when compared with the Myo-PWT control, although this did not reach statistical significance, which may reflect the small cohort sizes and the apparent antitumour effect observed in the Myo-PWT group.
The surviving mice whose tumours had completely regressed in both active treatment groups were subsequently rechallenged with the same colorectal cancer cells and monitored for up to 30 days. No tumour growth was observed in any of the mice during this period, consistent with a durable antitumour response.
Crucially, the Myo-P3 and systemic ipilimumab achieved these effects through very different delivery and dosing approaches. Ipilimumab was administered systemically by intraperitoneal injection at 10 mg/kg twice weekly for two weeks (400 μg/week for a 20 g mouse, corresponding to a nominal average of ~57 μg/day), whereas a single Myo-P3 was implanted subcutaneously adjacent to the established tumour to provide continuous, low-dose local secretion of the anti-CTLA-4 antibody. To quantify the amount of antibody delivered by the Myo-P3, secretion was measured before implantation and again in a separate group of tumour-bearing mice seven days later, when the devices were explanted and analysed. A single Myo-P3 secreted approximately 2.13 μg of anti-CTLA-4 antibody per day before implantation and 1.89 μg per day at explantation one week later, demonstrating comparable secretion capacity at the two time points. At the same seven-day time point, plasma anti-CTLA-4 antibody levels were significantly lower in Myo-P3-treated mice than in those receiving systemic ipilimumab.
This difference in systemic exposure is particularly relevant because, although ipilimumab is an approved cancer immunotherapy, systemic CTLA-4 blockade can be associated with potentially severe immune-related toxicities.4 No visible signs of immune-mediated cutaneous toxicity were observed in the Myo-P3, Myo-PWT or untreated control groups, compared with 42% of mice treated systemically with ipilimumab, which developed alopecia. While toxicity findings from mouse checkpoint-blockade studies cannot be directly extrapolated to humans, these results suggest that reducing systemic antibody exposure may help lower treatment-related toxicity.
The next question was whether this lower systemic exposure achieved with the Myo-P3 still translated into effective immune modulation within the tumour. Earlier studies have associated the antitumour activity of CTLA-4 blockade with greater infiltration of effector T cells into the tumour, where they can attack cancer cells, alongside reduced levels of Tregs, a subset of CD4+ T cells that can suppress antitumour immune activity.[6] In tumours analysed seven days after start of treatment, the Myo-P3 group showed a higher proportion of cytotoxic CD8+ T cells than the Myo-PWT group, consistent with a greater presence of cancer-fighting effector T cells within the tumour. This effect was more pronounced with systemic ipilimumab, which produced the highest proportion of intratumoural CD8+ T cells. Seven days after treatment, intratumoural Tregs were significantly reduced in the Myo-P3 group, to a similar extent as with systemic ipilimumab. Unlike systemic ipilimumab, however, the Myo-P3 did not significantly alter Treg levels in the tumour-draining lymph node or spleen, consistent with a more localised immune effect.
Taken together, these findings provided proof-of-concept that a single Myo-P3 implant could achieve antitumour activity and the expected local immune modulation in this model through sustained, low-dose anti-CTLA-4 delivery, while maintaining substantially lower systemic antibody exposure than systemic ipilimumab.
Longer-Term Evaluation of Sustained Local Anti-CTLA-4 Delivery
In the subsequent, longer-term dose-escalation study, designed to assess the tolerability of higher local anti-CTLA4 exposure, the researchers increased the Myo-P3 treatment from a single capsule to four adjoined capsules (the quadripod) implanted peritumourally, thereby increasing the amount of anti-CTLA-4 antibody available for local delivery.
Before implantation, the quadripod secreted approximately 7.16 μg of anti-CTLA-4 antibody per day, around 3.3-fold more than the single Myo-P3, with secretion measuring approximately 4.90 μg per day when the devices were explanted one week later. The comparator groups were the same as in the initial study (a Myo-PWT quadripod containing unmodified IHMs, systemic ipilimumab administered at 10 mg/kg twice weekly for two weeks, and untreated controls), with one additional group receiving a single 8 μg peritumoural injection of ipilimumab. Tumour growth and survival were followed for up to 104 days, with individual mice euthanised earlier if they reached the study’s tumour-burden endpoint. Circulating antibody levels were compared by measuring human IgG1 in plasma one week after treatment. At this time point, plasma antibody levels in mice treated with the Myo-P3 quadripod were approximately 29-fold lower than in mice receiving systemic ipilimumab, while levels following the single peritumoural administration of ipilimumab were lower still.
Mice treated with the Myo-P3 quadripod exhibited a statistically significant delay in tumour progression compared with untreated controls, consistent with the tumour-growth effect observed with the single Myo-P3 in the initial study. Long-term survival analysis also showed a statistically significant survival benefit for mice treated with the Myo-P3 quadripod or systemic ipilimumab compared with untreated controls.
At day 8, intratumoural Tregs were significantly lower in mice treated with either the Myo-P3 quadripod or systemic ipilimumab than in untreated or Myo-PWT controls. Human CTLA-4-positive cells among CD4+ T cells were also significantly reduced in both active treatment groups compared with the Myo-PWT group. Unexpectedly, on day 14, none of these immune-cell populations differed significantly between groups, suggesting that the intratumoural immune changes observed at day 8 were transient.
The longer-term study also showed a pattern of observable toxicity consistent with the initial study. No visible signs of immune-mediated cutaneous toxicity were observed in the Myo-P3 quadripod group, despite the higher and sustained local anti-CTLA-4 exposure provided by the quadripod compared with the initial study. No such toxicity was observed in the Myo-PWT quadripod or untreated groups either, compared with 50% of mice receiving systemic ipilimumab and 30% of those receiving the single peritumoural ipilimumab injection. Taken together, these findings suggest that where and how anti-CTLA-4 is delivered may be more important for tolerability than the amount delivered alone, with sustained, localised delivery potentially limiting systemic toxicity while retaining antitumour activity.
Beyond the in vivo findings, the Myo-P3 demonstrated sustained and functional antibody production in vitro, with encapsulated IHMs continuing to secrete anti-CTLA-4 antibody for at least 9 months. The antibody remained biologically active and showed an approximately 13-fold lower EC50 than commercial ipilimumab in a CTLA-4 blockade assay, although the basis for this difference was not established. In a separate experiment in immunocompetent mice, implantation of either a single Myo-P3 or quadripod produced no statistically significant changes in circulating immunoglobulin G (IgG) and immunoglobulin M (IgM) after 15 days, providing preliminary evidence that implantation did not elicit a measurably systemic antibody response over this period.
Expanding the Evidence Base for ECT
The new iScience publication extends the evidence base for Release Tx’s ECT beyond its earlier clinical use in personalised cancer immunotherapy. In this preclinical setting, the Myo-P3 demonstrated that engineered, encapsulated IHMs could provide sustained local delivery of a functional anti-CTLA-4 antibody, delaying tumor progression and delivering immune modulation within the tumour while substantially lowering systemic antibody exposure compared with systemic ipilimumab. Importantly, even at the higher local exposure achieved with the Myo-P3 quadripod, no visible signs of immune-mediated cutaneous toxicity were observed, supporting the potential significance of where and how anti-CTLA-4 is delivered, rather than the amount delivered alone. Unlike an administered antibody dose, the Myo-P3 implant is retrievable, providing an additional level of control over treatment exposure.
For Release Tx, the significance of the publication is twofold: it adds to the scientific evidence supporting the MVX-ONCO programme licensed to HUG and UNIGE in 2025 and, more broadly, expands the evidence base for ECT as a modality for sustained, localised delivery of diverse, potent therapeutic proteins.[7] Under the licensing agreement, HUG and UNIGE hold exclusive rights to advance the MVX-ONCO programme, including the anti-CTLA-4-secreting cell line and associated ECT evaluated in the new publication. Release Tx retains an exclusive option to reacquire rights to future developments arising from the programme, preserving strategic exposure to further oncology advances while the Company remains focused on its CNS pipeline.
Release Tx would like to congratulate and thank the researchers and teams across Release Tx, HUG and UNIGE whose contributions made this work possible and helped bring these findings to publication. We look forward to sharing further updates as we continue to advance our proprietary ECT platform in severe CNS disorders.
The Release Tx Team
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