Continuous vs Intermittent mTOR Blockade
Daily dosing keeps mTOR fully suppressed but drains immune reserve.
- ~95%: Daily dose mTOR block (sustained suppression)
- ~90%: Pulse dose peak block (transient suppression)
- 3–5 d: Immune recovery window (between pulses)
- mTORC1: Trial basis (Mannick et al. protocol)
Why pulse instead of continuous
Placeholder: intermittent dosing allows immune rebound between hits.
Trade-off overview
Placeholder: short peaks trade some efficacy for lower toxicity.
Placeholder: pulsed regimens preserve vaccine response better.
Weekly and Biweekly Pulse Schedules
A single dose is given once every 7 or 14 days.
- 7 d: Weekly interval (standard pulse)
- 14 d: Biweekly interval (lower-burden pulse)
- 5–10 mg: Typical dose (per pulse, oral)
- ~62 h: Half-life (sirolimus elimination)
Choosing the interval
Placeholder: interval length sets peak-to-trough inhibition swing.
Schedule adherence
Placeholder: fewer doses per month improves patient adherence.
Immune Function Recovery Between Doses
Lymphocyte activity rebounds as drug levels fall after each pulse.
- Day 3: T-cell rebound onset (post-dose)
- Day 7: Near-full recovery (weekly protocol)
- +20%: Vaccine response gain (vs continuous dosing)
- Day 5: Cytokine normalization (inflammatory markers)
Recovery kinetics
Placeholder: immune markers climb back as mTOR block fades.
Functional readouts
Placeholder: vaccine antibody titers improve with recovery windows.
Placeholder: rest periods restore measurable immune competence.
Balancing Efficacy Against Side Effects
Higher frequency raises efficacy but also raises adverse event risk.
- Moderate: Weekly side-effect rate (mouth ulcers, lipids)
- Lower: Biweekly side-effect rate (reduced exposure)
- ~10%: Efficacy loss (biweekly) (vs weekly pulses)
- 4–6 wk: Monitoring interval (labs and trough levels)
The dosing trade-off curve
Placeholder: more frequent pulses trade tolerability for potency.
Common adverse effects
Placeholder: stomatitis, dyslipidemia, mild cytopenia are tracked.
Individualized Dose Titration
Dose and interval are tuned per patient using trough levels.
- 5–15 ng/mL: Trough target (individualized range)
- 2–4: Titration steps (visits to steady state)
- ±20%: Dose adjustment (per titration step)
- ~70%: Responder rate (reach target window)
Personalizing the protocol
Placeholder: labs guide dose and interval adjustments over time.
Long-term monitoring
Placeholder: periodic review keeps the regimen matched to response.
Placeholder: individualized titration optimizes benefit and safety.