Glycan-costumed virus-like particles promote type 1 anti-tumor immunity.

Cancer vaccine development is inhibited by a lack of strategies for directing dendritic cell (DC) induction of effective tumor-specific cellular immunity. Pathogen engagement of DC lectins and toll-like receptors (TLRs) shapes immunity by directing T cell function. Strategies to activate specific DC signaling pathways via targeted receptor engagement are crucial to unlocking type 1 cellular immunity. Here, we engineered a glycan-costumed virus-like particle (VLP) vaccine that delivers programmable peptide antigens to induce tumor-specific cellular immunity in vivo. VLPs encapsulating TLR7 agonists and decorated with a selective mannose-derived ligand for the lectin DC-SIGN induced robust DC activation and type 1 cellular immunity, whereas VLPs lacking this key DC-SIGN ligand failed to promote DC-mediated immunity. Vaccination with glycan-costumed VLPs generated tumor antigen-specific Th1 CD4+ and CD8+ T cells that infiltrated solid tumors, inhibiting tumor growth in a murine melanoma model. Thus, VLPs employing lectin-driven immune reprogramming provide a framework for advancing cancer immunotherapies.

Spatiotemporal encoding MRI using subspace-constrained sampling and locally-low-rank regularization: Applications to diffusion weighted and diffusion kurtosis imaging of human brain and prostate.

The benefits of performing locally low-rank (LLR) reconstructions on subsampled diffusion weighted and diffusion kurtosis imaging data employing spatiotemporal encoding (SPEN) methods, is investigated. SPEN allows for self-referenced correction of motion-induced phase errors in case of interleaved diffusion-oriented acquisitions, and allows one to overcome distortions otherwise observed along EPI's phase-encoded dimension. In combination with LLR-based reconstructions of the pooled imaging data and with a joint subsampling of b-weighted and interleaved images, additional improvements in terms of sensitivity as well as shortened acquisition times are demonstrated, without noticeable penalties. Details on how the LLR-regularized, subspace-constrained image reconstructions were adapted to SPEN are given; the improvements introduced by adopting these reconstruction frameworks for the accelerated acquisition of diffusivity and of kurtosis imaging data in both relatively homogeneous regions like the human brain and in more challenging regions like the human prostate, are presented and discussed within the context of similar efforts in the field.