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Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines. The T-cell-mediated pAXL×CD3ε cytotoxicity against sarcoma cells was investigated by flow cytometry, luminescence assay, and fluorescent microscopy imaging. The activation and degranulation of T cells induced by pAXL×CD3ε were evaluated by flow cytometry. The antitumor activity induced by pAXL×CD3ε in combination with trabectedin was also investigated. In vivo activity studies of pAXL×CD3ε were performed in immunocompromised mice (NSG), engrafted with human sarcoma cells and reconstituted with human peripheral blood mononuclear cells from healthy donors. Most sarcoma cells showed high expression of AXL. pAXL×CD3ε triggered T-lymphocyte activation and induced dose-dependent T-cell-mediated cytotoxicity. The combination of pAXL×CD3ε with trabectedin increased cytotoxicity. pAXL×CD3ε inhibited the in vivo growth of human sarcoma xenografts, increasing the survival of treated mice. Our data demonstrate the antitumor efficacy of pAXL×CD3ε against sarcoma cells, providing a translational framework for the clinical development of pAXL×CD3ε in the treatment of human sarcomas, aggressive and still-incurable malignancies.

Biocompatible Pickering emulsions (PE) stabilized by tailor-made antioxidant-loaded particles have been known for some time now, but antioxidant-rich natural plant particle-based emulsions are much less well known. This study aimed to investigate the physico-chemical properties of commercial Zingiber officinale powders obtained from biological and conventional agricultural practice and ginger powder-based PE.The physico-chemical and biological properties of Zingiber officinale powders (GDPs) obtained from conventional (GDPC1 and GDPC2) and biological agricultural (GDPBIO) practices, and the properties of derived PE (PE_GDPs) were examined. All GDPs showed weak aggregation in aqueous media and a sufficiently hydrophobic surface to stabilize oil-in-water (O/W) PE against coalescence for at least 1 month. Zingiber officinale powders (2% w/w) derived from biological agricultural practices (GDPBIO) demonstrated the best emulsifying properties. The Zingiber officinale powders and PE_GDPs were also characterized by their phytochemical profiles. All the investigated samples exhibited ferric reducing ability power greater than the positive control, butylated hydroxytoluene (BHT), with values ranging from 91.21 to 102.63 μmol LThe results suggest that ginger powder should be used as a starting point to design biocompatible PEs for different applications in the functional food, nutraceutical, and pharmaceutical industries. In fact, powder and based PE are characterized by a promising antioxidant activity, carbohydrate hydrolyzing enzyme and lipase inhibitory properties. Further in vivo studies are necessary to confirm these findings. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John WileySons Ltd on behalf of Society of Chemical Industry.

Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines. The T-cell-mediated pAXL×CD3ε cytotoxicity against sarcoma cells was investigated by flow cytometry, luminescence assay, and fluorescent microscopy imaging. The activation and degranulation of T cells induced by pAXL×CD3ε were evaluated by flow cytometry. The antitumor activity induced by pAXL×CD3ε in combination with trabectedin was also investigated. In vivo activity studies of pAXL×CD3ε were performed in immunocompromised mice (NSG), engrafted with human sarcoma cells and reconstituted with human peripheral blood mononuclear cells from healthy donors. Most sarcoma cells showed high expression of AXL. pAXL×CD3ε triggered T-lymphocyte activation and induced dose-dependent T-cell-mediated cytotoxicity. The combination of pAXL×CD3ε with trabectedin increased cytotoxicity. pAXL×CD3ε inhibited the in vivo growth of human sarcoma xenografts, increasing the survival of treated mice. Our data demonstrate the antitumor efficacy of pAXL×CD3ε against sarcoma cells, providing a translational framework for the clinical development of pAXL×CD3ε in the treatment of human sarcomas, aggressive and still-incurable malignancies.