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Preprint WatchModerateSeptember 23rd, 2026

Dual Immunoliposome Targeting of PD-L1 and CSF1R affects T-Cell readouts in tumor-conditioned co-cultures: An In Vitro Study in Glioblastoma and Medulloblastoma

Asad Pour, O.; Asadpour, A.; Ghanam, J.; Best, J.; Rahbarizadeh, F.; Hetze, S.; Chetty, V. K.; Barthel, L.; Amoozgar, Z.; Schmidt, H. H.; Thakur, B. K.

Immunoliposomes co-targeting PD-L1 and CSF1R on M2-like tumour-associated macrophages improve T-cell proliferation, survival and migration in tumour-conditioned co-cultures of glioblastoma and medulloblastoma.

Moderate contradiction

2 prior failures

Two documented clinical failures match this mechanism, or a single Phase 3 failure is on record.

This in vitro study argues that dual PD-L1 and CSF1R engagement on tumour-associated macrophages can restore T-cell function in brain tumour models. Claidex holds two CD274 post-mortems, and one of them sits directly on this indication. In avelumab-lenvatinib-cd274-pediatric-cns-tumors-phase1-efficacy-failure, PD-L1 blockade combined with a multikinase inhibitor failed on efficacy in paediatric primary high-grade CNS tumours, the same compartment and broadly the same immunosuppressed microenvironment this preprint models. The second entry, incb099280-cd274-oral-pd-l1-solid-tumors-phase1-strategic-discontinuation, records an oral PD-L1 inhibitor discontinued in solid tumours. The preprint's own framing concedes the relevant point, noting that single-target therapies have shown inconsistent results in brain tumours, and its proposed remedy is a second target rather than better delivery of the first. The flag is graded MODERATE because a recorded efficacy failure already exists at this target in this tissue. The readout here is Jurkat T cells in conditioned medium, which is several steps removed from the paediatric CNS setting where the clinical failure occurred, and the authors state that primary human macrophages and in vivo work are still needed.

Abstract excerpt

Glioblastoma and medulloblastoma are characterized by an immunosuppressive tumor microenvironment, in which tumor-associated macrophages may impair T-cell function, in part through the expression of PD-L1 and CSF1R. Single-target therapies have shown inconsistent results in brain tumors, likely due to the complex interplay involving tumor-associated macrophages and immunosuppression. We developed two immunoliposomes functionalized with antibodies against PD-L1 and CSF1R to co-target these receptors on M2-like tumor-associated macrophages. TAM2Ms were generated by polarizing THP-1 monocytes with glioblastoma (A172, U87MG) and medulloblastoma (DAOY, ONS-76) tumor-conditioned medium together with IL-4 and IL-13. In co-culture with activated Jurkat T cells under tumor-conditioned medium-influenced conditions, combined PD-L1 and CSF1R immunoliposomes enhanced T-cell proliferation, reduced apoptosis, and improved migration toward tumor spheroids compared to single-target liposomal treatments or free antibodies. These benefits varied between glioblastoma and medulloblastoma in vitro models, reflecting distinct TAM2M phenotypes and microenvironment contexts. Dual immunoliposome targeting of PD-L1 and CSF1R may offer a promising strategy for reprogramming tumor-associated macrophages in brain tumor immunotherapy and warrants further evaluation in primary human macrophages and in vivo models to clarify efficacy and mechanisms.

Matching Claidex post-mortems

2 of 2 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.