No abstract

Personalized cancer vaccines (PCVs) targeting patient-specific neoantigens are a promising cancer treatment modality; however, neoantigen physicochemical variability can present challenges to manufacturing PCVs in an optimal format for inducing anticancer T cells. Here, we developed a vaccine platform ("SNP-7/8a") based on charge-modified peptide-TLR-7/8a conjugates that are chemically programmed to self-assemble into nanoparticles of uniform size (~20 nm) irrespective of the peptide antigen composition. This approach provided precise loading of diverse peptide neoantigens linked to TLR-7/8a (adjuvant) in nanoparticles that increased uptake by and activation of antigen-presenting cells that promote T cell immunity. Vaccination of mice with SNP-7/8a using predicted neoantigens (n=179) from three tumor models induced CD8 T cells against ~50% of neoantigens with high predicted MHC-I binding affinity and led to enhanced tumor clearance. SNP-7/8a delivering in silico-designed mock neoantigens also induced CD8 T cells in non-human primates. Altogether, SNP-7/8a is a generalizable approach for co-delivering peptide antigens and adjuvants in nanoparticles for inducing anticancer T cell immunity.

We demonstrate the alignment of multiwalled carbon nanotubes in bulk epoxy matrices by application of external electric field. The composites were prepared by a macro-layer-by-layer method; UV light was used to rapidly polymerize the epoxy and preserve the aligned nanotube network. The nanotube alignment generated strong anisotropy in the composite’s properties. The composite’s storage modulus was increased by ∼50%, and the electrical conductivity was improved by four orders of magnitude in the direction of nanotube alignment. Compared to pristine nanotubes, amine functionalized nanotubes showed enhanced storage modulus but reduced electrical conductivty. The enhanced modulus for amine functionalized nanotubes is an artifact of their enhanced compatibility with the epoxy, while their reduced conductivity may result from the shortening of the nanotube length during functionalization. In addition to the rapid alignment of nanotubes parallel to the field direction, we also report a tendency for lateral agglomeration (perpendicular to the field) of the aligned nanotubes over time. Such a coarsening effect can be mitigated by minimizing the polymerization (or cure) time of the epoxy.

No abstract

New dual initiators, 3,3,5-trimethyl-5-chlorohexyl 2-bromopropionate (IB2BP) and 3,3,5-trimethyl-5-chlorohexyl 2-bromo-2-methylpropionate (IB2BMP), which contain initiating sites for both carbocationic polymerization and atom transfer radical polymerization (ATRP), were synthesized and used to create poly(isobutylene-b-methyl acrylate) (PIB-b-PMA) diblock copolymers. Initiator synthesis involved reaction of methyl 3,3-dimethyl-4-pentenoate with 2 equiv of methylmagnesium bromide, followed by hydroboration−oxidation of the double bond to yield 1,5-dihydroxy-3,3,5-trimethylhexane (DHTMH). IB2BP was synthesized by reaction of the primary hydroxyl group of DHTMH with 2-bromopropionyl bromide, followed by chlorination of the tertiary hydroxyl group with anhydrous HCl. IB2BMP was synthesized analogously using 2-bromo-2-methylpropionyl bromide. Both initiators displayed slow cationic initiation of isobutylene, leading to moderate initiation efficiencies (0.50 < I eff < 0.80) at low temperature (−70 °C) and low monomer/initiator ratio (82). Higher cationic initiation efficiency (0.80 < I eff < 0.90) was observed when temperature was increased to −50 °C and/or the monomer/initiator ratio was increased. In spite of low I eff, the resulting PIBs had narrow polydispersity, and each chain contained one intact 2-bromopropionyl head group, which was subsequently used for ATRP of methyl acrylate. Efficiency of radical initiation was very high, and targeted PMA block lengths were obtained.