CD40L-GVAX(University of South Florida)

The GM.CD40L vaccine, which recruits and activates dendritic cells, migrates to lymph nodes, activating T cells and leading to systemic tumor cell killing. When combined with the CCL21 chemokine, which recruits T cells and enhances T-cell responses, additive effects have been demonstrated in non-small cell lung cancer mouse models. Here, we compared GM.CD40L versus GM.CD40L plus CCL21 (GM.CD40L.CCL21) in lung adenocarcinoma patients with ≥ 1 line of treatment. In this phase I/II randomized trial (NCT01433172), patients received intradermal vaccines every 14 days (3 doses) and then monthly (3 doses). A two-stage minimax design was used. During phase I, no dose-limiting toxicities were shown in three patients who received GM.CD40L.CCL21. During phase II, of evaluable patients, 5/33 patients (15.2%) randomized for GM.DCD40L (p = .023) and 3/32 patients (9.4%) randomized for GM.DCD40L.CCL21 (p = .20) showed 6-month progression-free survival. Median overall survival was 9.3 versus 9.5 months with GM.DCD40L versus GM.DCD40L.CCL21 (95% CI 0.70-2.25; p = .44). For GM.CD40L versus GM.CD40L.CCL21, the most common treatment-related adverse events (TRAEs) were grade 1/2 injection site reaction (51.4% versus 61.1%) and grade 1/2 fatigue (35.1% versus 47.2%). Grade 1 immune-mediated TRAEs were isolated to skin. No patients showed evidence of pseudo-progression or immune-related TRAEs of grade 1 or greater of pneumonitis, endocrinopathy, or colitis, and none discontinued treatment due to toxicity. Although we found no significant associations between vaccine immunogenicity and outcomes, in limited biopsies, one patient treated with GMCD40L.CCL21 displayed abundant tumor-infiltrating lymphocytes. This possible effectiveness warrants further investigation of GM.CD40L in combination approaches.

Magnetic nanoparticles NiFe₂O₄ was synthesized and covered in the silicate lattice of (3-Aminopropyl) triethoxysilane (APS) by the sol-gel process. Subsequently, the EDTA-dianhydride was attached to the amino surface of magnetic nanoparticles (MNPs) during the nucleophilic attack. This polycarboxylic layer trapped the high level of nickel ions for selective bonding to the His-tagged recombinant protein. The surface of MNPs was investigated by TEM, XRD, SEM (EDSA), VSM, BET, FT-IR and zeta potential analysis which characterized the size, chemical lattice, morphology, magnetic strength, specific surface area, functional groups and charge of the surface of nanoparticles. The performance and validity of the nanoparticles were studied by the purification of His-tagged green fluorescence protein (His-GFP). Also, the safety of proposed Ni-MNPs in the purification procedure of His-tagged proteins for pharmaceutical applications was proved by the determination of the nickel leakage level in the purified final protein using atomic absorption spectroscopy. In vitro cytotoxicity of Ni-MNPs and trace metal ions was investigated by the MTS assay technique. In addition, the comparison of biological activity in purified protein (GM-CSF) and commercial sample did not show any toxic effect.