ALT An illustrated diagram from the editorial "Science behind the Study: Optogenetics in Sight" that shows direct and indirect translational optogenetics pathways. Panel A: Precise identification of causal cells and circuits allows principled targeting, whether through direct (left), indirect neuromodulatory (middle), or indirect medicinal (right) approaches. Panel B: Components of direct optogenetics for retinitis pigmentosa are shown, including the adeno-associated virus (AAV) (top), the light-projecting goggles (middle), and the channelrhodopsin protein (bottom). The NEJM identity sits at the bottom.

ALT This image contains four graphs. Panels A and B show progression-free survival and overall survival among all patients who received anitocabtagene autoleucel (anito-cel), a B-cell maturation antigen (BCMA)–directed autologous chimeric antigen receptor (CAR) T-cell therapy with a synthetic D-domain binder (ddBCMA). Panels C and D show progression-free survival among patients according to the presence or absence of extramedullary disease (EMD) and according to the β2-microglobulin (β2M) level (≥5.5 or <5.5 mg per liter), respectively.

ALT This image contains five graphs. Panel A shows anito-cel vector transgene levels in peripheral blood per microgram of genomic DNA (gDNA). Panels B–E show changes in serum soluble BCMA levels and in concentrations of CAR T-cell activation–associated serum analytes interferon-γ, interleukin-2, and interleukin-6 that were evaluated at baseline and after the anito-cel infusion.

ALT This image contains four figures. Panel A shows the size and structure of the dual variable heavy-chain domain of a heavy chain–only antibody (dual-VHH) and ddBCMA binders and biolayer interferometry binding data demonstrating strong avidity effects for the dual-VHH binder, whereas no avidity effect was observed with the ddBCMA binder. Panel B shows a schematic of the research-grade CAR constructs expressed in T cells and used in subsequent experiments. Panel C shows immune synapse formation between ddBCMA CAR or dual-VHH CAR T cells and BCMA-expressing K562 cells as assessed by imaging flow cytometry. Panel D shows cytotoxicity (the percentage of tumor cells killed) and cytokine release values (granulocyte–macrophage colony-stimulating factor [GM-CSF], interleukin-2, and interferon-γ) with primary bone marrow mononuclear cells from patients with multiple myeloma after coculture with ddBCMA CAR T cells or dual-VHH CAR T cells, with technical replicates shown as means.

ALT A graph from an Original Article published in the New England Journal of Medicine article titled "Phase 1 Study of Anito-cel, a D-Domain BCMA CAR T Cell for Refractory or Recurrent Myeloma." The graph shows progression-free survival among all patients who received anito-cel. The NEJM identity sits at the bottom.