Biology subjects

Heitmann, J.

Publications and source records attributed to Heitmann, J..

3 recordsLinked to original sources

bioRxiv2026

Bivalent bispecific CD28 antibodies reinforce T-cell responsiveness and revert anergy/quiescence in patients treated with bispecific CD3 antibodies

Bispecific T-cell engagers stimulating CD3 (TCEs) rapidly gain momentum in oncological therapy. We report that single-agent TCE-treatment of cancer patients induces T cell hyporesponsiveness including abolished proliferative and lytic capacity. Single-cell RNA-sequencing identified transcriptional features of anergy/quiescence like upregulation of CBLB and BACH2, and suppression of AP 1-dependent activation programs due to isolated provision of T cell signal-1. To restore T cell functionality, we engineered bispecific costimulators (BiCos) which deliver signal-2 via highly efficient bivalent CD28-binding yet maintain strictly target-restricted activity after binding antigens expressed not only by tumor cells but also the extracellular matrix. Preclinical analyses documented that BiCos potentiate efficacy of single-agent TCE treatment with activity exceeding that of univalent Knob-into-Hole CD28-costimulators and revert T cell hyporesponsiveness. In humanized mice, BiCos induced elimination of established tumors in combination with very low doses of TCE. Finally, BiCos reversed molecular hallmark features of quiescence such as high expression of BACH2 and KLF2 in T cells of TCE-treated patients resulting in complete restoration of cellular function, thereby reinstating durable antitumor immunity.

immunology↗

bioRxiv2026

Balancing Lucidity: Muscle and Vestibular Stimulation for Lucid Dream Induction

Lucid dream (LD) induction using external sensory stimulation has most commonly relied on distal cues such as lights or auditory signals, with mixed success rates. In this study, we investigated whether more direct bodily stimulation targeting the muscle and vestibular systems could influence LD induction. We compared electrical muscle stimulation (EMS) and galvanic vestibular stimulation (GVS), each combined with a two-week cognitive training protocol including dream journaling, reality checks, and association training. Twenty-eight participants (14 per group) completed two counterbalanced morning naps: one with stimulation (STIM) during REM sleep and with one sham-stimulation control (SHAM). EMS and GVS stimulation did not lead to increased incorporation of the stimulus. Lucidity rates were high in both EMS conditions, highlighting the substantial role of elevated baseline lucidity in induction studies, cognitive training, and expectation effects. In contrast, GVS stimulation significantly increased externally rated lucidity and DLQ questionnaire scores compared to control. Overall, the findings indicate that galvanic vestibular stimulation can increase dream lucidity. Future work should further examine the mechanisms by which vestibular stimulation influences dream awareness and its potential role in lucid dream induction. O_FIG O_LINKSMALLFIG WIDTH=191 HEIGHT=200 SRC="FIGDIR/small/711028v1_ufig1.gif" ALT="Figure 1"> View larger version (86K): org.highwire.dtl.DTLVardef@7de78forg.highwire.dtl.DTLVardef@1ed7628org.highwire.dtl.DTLVardef@e84964org.highwire.dtl.DTLVardef@2a5f5e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2026

Waking Up in the Dream Lab: A Lab-Based Lucid Dream Induction Paradigm Using Virtual Reality and Sensory Stimulation

Lucid dreaming (LD), during which the dreamer is aware that they are dreaming, is frequently induced in laboratory settings by delivering sensory cues during rapid eye movement (REM) sleep. These cues should be incorporated into ongoing dreams and can trigger reflective awareness. This approach relies on the continuity between waking experiences and dream content. In sleep laboratories, participants often dream of the experimental setting itself (lab dreaming), providing a predictable context in which lucidity may emerge. The present studies leveraged this phenomenon by explicitly training participants to associate the sleep laboratory with reflective awareness prior to sleep. Across three studies (total N = 101), participants completed a morning nap following verbal LD instructions and presleep audio designed to prime recognition of the laboratory context in dreams. In addition, conditions included immersive virtual reality (VR) rehearsal of the laboratory environment, VR combined with haptic stimulation (HS) during REM sleep, or VR containing subtle fake system errors intended to prompt reflective checking. LD frequency was assessed through external ratings of signal-verified LD (SVLD) dream reports. Lucidity rates were high across all conditions, with approximately 40-45% of dreams externally rated as lucid and 11%-32% SVLDs occurring in every group. However, neither VR rehearsal, haptic stimulation, nor implicit VR errors increased lucidity relative to the baseline laboratory induction procedure. Exploratory analyses investigated the overlap between laboratory dreaming, false awakenings (FAs), and lucidity. These findings suggest that explicit training focused on the predictable context of the sleep laboratory may already provide a powerful pathway to lucidity, with additional technological manipulations offering limited benefit under a single-nap protocol. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/711049v2_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@8f2327org.highwire.dtl.DTLVardef@14cfbaeorg.highwire.dtl.DTLVardef@11f9bbforg.highwire.dtl.DTLVardef@2a57bf_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗