ArticleCancer research communications2026
Clinical Evaluation of Ex Vivo Expanded MUC1-Specific Peripheral Blood T Cells for Adoptive Immunotherapy in Relapsed/Refractory Multiple Myeloma.
Article in Cancer research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05411497 (Use of Natural Signals and Ambient Dendritic Cells to Culture-Expand Cancer Targeting T-Cells Directly From Unfractionated Peripheral Blood), which is not on this map. Not yet cited in PubMed.
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Use of Natural Signals and Ambient Dendritic Cells to Culture-Expand Cancer Targeting T-Cells Directly From Unfractionated Peripheral Blood: A Phase 1 T-Cell Dose Escalation Trial Targeting Relapsed and Refractory MUC1-Expressing Multiple Myeloma
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Abstract
purposeNaturally occurring tumor-specific T cells derived from peripheral blood (PB) offer a clinically accessible source for adoptive immunotherapy. However, the expansion of these T cells from patients with cancer remains a challenge. We hypothesized that mimicking innate immune activation could optimally stimulate antigen-driven T-cell expansion in vitro, unlocking the therapeutic potential of PB-derived T cells. PATIENTS AND
methodsWe previously developed an ex vivo culture system that selectively expands tumor antigen-activated T cells from PB mononuclear cells (PBMC), generating multiclonal effector and central memory T cells. In this hypothesis-generating study, we evaluated the therapeutic potential of MUC1-activated T cells in patients with relapsed and/or refractory multiple myeloma (r/rMM) in a phase I clinical trial (NCT05411497). MUC1 is an oncoprotein overexpressed in r/rMM. We translated our small-scale culture into GMP-compliant, large-scale manufacturing, which achieved expansion of T cells from heavily pretreated patients' PBMCs without exhaustion. Five patients were treated with escalating doses of up to 1 × 1010 T cells.
resultsAlthough the cell infusions were well tolerated, no objective responses occurred. One patient, who received the highest dose, has had stable disease for 2 years after infusion. This patient exhibited transient dermatitis with localized MUC1 and CD3 staining, as potential evidence of on-target, off-tumor T-cell reactivity, perhaps contributing to disease stabilization. T-cell receptor sequencing revealed the T-cell product in four of the patients' blood, which correlated with the product's degree of polyfunctionality and MUC1 reactivity.
conclusionsThese findings demonstrate the feasibility, safety, and biological activity of PB-derived, MUC1-specific T cells as adoptive immunotherapy. SIGNIFICANCE: Expanding tumor antigen-specific T cells for clinical use from the blood of heavily pretreated patients with cancer remains a significant hurdle. We scale up a novel culture method that integrates innate immune signals to stimulate T-cell expansion and demonstrate safety, feasibility, and a case of long-term disease stabilization upon treatment of patients with multiple myeloma in a phase I clinical trial.
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