Search

Abstract Neoantigen-specific T cell receptors (neoTCRs) promise safe, personalized anti-tumor immunotherapy. However, detailed assessment of neoTCR-characteristics affecting therapeutic efficacy is mostly missing. Previously, we identified diverse neoTCRs restricted to different neoantigens in a melanoma patient. In this work, we now combine single-cell TCR-sequencing and RNA-sequencing after neoantigen-specific restimulation of peripheral blood-derived CD8+ T cells of this patient. We detect neoTCRs with specificity for the previously detected neoantigens and perform fine-characterization of neoTCR-transgenic (tg) T cells in vitro and in vivo. We describe a heterogeneous spectrum of TCR-intrinsic activation patterns in response to a shared neoepitope ranging from previously detected more highly frequent neoTCRs with moderate activation to rare ones with initially stronger activation. Experimental restimulation of adoptively transferred neoTCR-tg T cells in a xenogeneic rechallenge tumor model demonstrates superior anti-tumor responses of moderate neoTCR-tg T cells upon repeated tumor contact. These insights have significant implications for the selection of TCRs for therapeutic engineering of TCR-tg T cells.

Increasing the rigidity of a macromolecule while maintaining solubility is challenging. Here, the authors demonstrate covalent connection of two rigid-rod polymer chains with stiff connectors, leading to rigid ladder structures with well-defined conjugated rails.

Photon antibunching typically measures the time-averaged photophysics of multichromophoric nanoparticles. Here, the authors report on time-resolving photon antibunching, allowing the true number of chromophores and exciton diffusion to be measured in DNA origami and conjugated polymer aggregates.

The ultrafast optical dynamics of plasmon-quantum emitter systems have rarely been explored. Here, the authors study those dynamics by interferometrically probing nonlinear optical emission from porous gold nanosponges with zinc oxide emitters, allowing sum-frequency generation enhancement from individual hot spots.

Coherent coupling in soft matter, controlled by nanoscale morphology, plays an important role in charge generation and recombination in optoelectronics. Eder et al. show how to reversibly switch between H- and J-type coupling in conjugated polymer aggregates, leading to tunable photoluminescence.