Michael F. Cuccarese

TL;DR: The ability of rationally engineered drug–nanoparticle combinations to efficiently modulate tumour-associated macrophages for cancer immunotherapy is demonstrated and R848, an agonist of the toll-like receptors TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro.

TL;DR: In vivo imaging is used to uncover the fate and activity of aPD-1 mAbs and identify specific Fc/FcγR interactions that can be modulated to improve checkpoint blockade therapy.

TL;DR: It is shown that the tumor microenvironment itself can be therapeutically primed to facilitate accumulation of multiple clinically relevant TNPs, and it is demonstrated that local tumor irradiation substantially increases TAM relative to tumor cells and, thus, TNP delivery.

TL;DR: This method reveals that TAM density was heterogeneous across tumours in the same animal, overall TAM density is different among separate pulmonary tumour models, nanotherapeutic drug delivery correlated with TAM heterogeneity, and successful response to CSF-1R blockade is characterized by enhanced TAM penetration throughout and within tumours.

TL;DR: This work quantitated the dynamics of target engagement of covalent BTK inhibitors, as well as reversible PARP inhibitors, in populations of single cells using a single companion imaging probe for each target and determined average in vivo tumor concentrations.