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Publications

Journal Article Epublish

PubMed: 40427155 DOI: 10.3390/cancers17101658

Beyond Exosomes: An Ultrapurified Phospholipoproteic Complex (PLPC) as a Scalable Immunomodulatory Platform for Reprogramming Immune Suppression in Metastatic Cancer.

Cancers (Basel) 17(10)

Authors: Ramon Gutierrez-Sandoval, Francisco Gutiérrez-Castro, Natalia Muñoz-Godoy, Ider Rivadeneira, Adolay Sobarzo, Jordan Iturra, Francisco Krakowiak, Luis Alarcón, Wilson Dorado, Andy Lagos, Diego Montenegro, Ignacio Muñoz, Rodrigo Aguilera, Andres Toledo

Affiliations

  • Department of Oncopathology, OGRD Alliance, Lewes, DE 19958, USA.
  • Department of Cancer Research, Flowinmunocell-Bioexocell Group, 08028 Barcelona, Spain.
  • Department of Outreach and Engagement Programs, OGRD Consortium, Charlestown KN0802, Saint Kitts and Nevis.
  • Departmento de Ciencias Biológicas y Químicas, Facultad de Medicina y Ciencia, Universidad San Sebastián, Concepción 4080871, Chile.
  • Department of Outreach and Engagement Programs, OGRD Consortium, Charlestown KN0802, Saint Kitts and Nevis. Department of Molecular Oncopathology, Bioclas, Concepción 4030000, Chile.

Abstract

Background/Objectives: Dendritic-cell-derived exosomes (DEXs) have demonstrated immunostimulatory potential in cancer immunotherapy, yet their clinical application remains constrained by their cryodependence, compositional heterogeneity, and limited scalability. To address these limitations, we developed an ultrapurified phospholipoproteic complex (PLPC), a dendritic-secretome-derived formulation stabilized through ultracentrifugation and lyophilization that has been engineered to preserve its immunological function and structural integrity. Methods: Secretomes were processed under four conditions (fresh, concentrated, cryopreserved, and lyophilized PLPC) and compared through proteomic and functional profiling. Mass spectrometry (LC-MS/MS) analysis revealed that the PLPC retained a significantly enriched set of immunoregulatory proteins-including QSOX1, CCL22, and SDCBP-and exhibited superior preservation of post-translational modifications. Results: Ex vivo co-culture assays with human peripheral blood mononuclear cells (PBMCs) demonstrated that the PLPC induced robust secretion of IFN-γ, TNF-α, and IL-6 while concurrently suppressing IL-10, achieving an IFN-γ/IL-10 ratio exceeding 3.5. Flow cytometry confirmed the substantial activation of both CD4⁺ and CD8⁺ T cells, while apoptosis assays showed selective tumor cytotoxicity (>55% tumor apoptosis) with minimal impact on non-malignant cells (>92% viability). Conclusions: These findings establish the PLPC as a reproducible, Th1-polarizing immunomodulator with selective antitumor activity, ambient-temperature stability, and compatibility with non-invasive administration. Overall, the PLPC emerges as a scalable, cell-free immunotherapeutic platform with translational potential to reprogram immune suppression in metastatic therapy-resistant cancer settings.

MeSH

Cells, Tumor Escape, Neoplasms, Exosomes, Therapeutics, Apoptosis

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