Investigating Two Modes of Cancer-Associated Antigen Heterogeneity in an Agent-Based Model of Chimeric Antigen Receptor T-Cell Therapy.

Chimeric antigen receptor (CAR) T-cell therapy has been successful in treating liquid tumors but has had limited success in solid tumors. This work examines unanswered questions regarding CAR T-cell therapy using computational modeling, such as, what percentage of the tumor must express cancer-associated antigens for treatment to be successful? The model includes cancer cell and vascular and CAR T-cell modules that interact with each other. We compare two different models of antigen expression on tumor cells, binary (in which cancer cells are either susceptible or are immune to CAR T-cell therapy) and gradated (where each cancer cell has a probability of being killed by a CAR T-cell). We vary the antigen expression levels within the tumor and determine how effective each treatment is for the two models. The simulations show that the gradated antigen model eliminates the tumor under more parameter values than the binary model. Under both models, shielding, in which the low/non-antigen-expressing cells protect high antigen-expressing cells, reduced the efficacy of CAR T-cell therapy. One prediction is that a combination of CAR T-cell therapies that targets the general population of cells as well as one that specifically targets cancer stem cells should increase its efficacy.

Engineering Efficient Photon Upconversion in Semiconductor Heterostructures.

Photon upconversion is a photophysical process in which two low-energy photons are converted into one high-energy photon. Photon upconversion has broad appeal for a range of applications from biomedical imaging and targeted drug release to solar energy harvesting. Current upconversion nanosystems, including lanthanide-doped nanocrystals and triplet-triplet annihilation molecules, have achieved upconversion quantum yields on the order of 10-30%. However, the performance of these materials is hampered by inherently narrow absorption cross sections and fixed energy levels originating in atomic, ionic, or molecular states. Semiconductors, on the other hand, have inherently wide absorption cross sections. Moreover, recent advances enable the synthesis of colloidal semiconductor nanoparticles with complex heterostructures that can control band alignments and tune optical properties. We synthesize and characterize a three-component heterostructure that successfully upconverts photons under continuous-wave illumination and solar-relevant photon fluxes. The heterostructure is composed of two cadmium selenide quantum dots (QDs), an absorber and emitter, spatially separated by a cadmium sulfide nanorod (NR). We demonstrate that the principles of semiconductor heterostructure engineering can be applied to engineer improved upconversion efficiency. We first eliminate electron trap states near the surface of the absorbing QD and then tailor the band gap of the NR such that charge carriers are funneled to the emitting QD. When combined, these two changes result in a 100-fold improvement in photon upconversion performance.