# Fever Inspiration: Precision Engineering for Safe and Systemic Immunotherapy

## TL;DR

This paper explores engineered fever therapy as a new cancer treatment that uses fever to boost the immune system, combining nanotechnology and precision engineering for safer and more effective results.

## Contribution

The paper introduces a bioengineered framework for controllable fever induction with precise temperature control and immune pathway modulation.

## Key findings

- Engineered fever therapy can activate systemic immune responses by inducing fever-range temperatures in tumors.
- Nanotechnology enables targeted and safe thermal immunotherapy with optimized fever dynamics.
- The therapy's clinical translation faces challenges but offers promising opportunities in precision oncology.

## Abstract

Fever, a conserved physiological response, orchestrates robust immunomodulation with significant therapeutic potential. Engineered fever therapy (EFT) leverages this mechanism to activate systemic immune response, emerging as a transformative adjuvant strategy for disease management, particularly in oncology. However, achieving precise and safe EFT remains challenging, largely due to unpredictable temperature fluctuations and inconsistent immune responses. To address these limitations, thermal immunotherapy integrates precision thermal modulation with nanotechnology, enabling targeted induction of fever‐range temperatures (38.5–40 °C) within tumor sites. Building upon physiological fever mechanisms and precision bioengineering, controllable EFT establishes a new paradigm with three core principles: i) precise fever induction with input and process control, ii) quantitative reprogramming of immune pathways, and iii) enhanced safety through optimized fever dynamics. This review comprehensively summarizes the molecular and physiological underpinnings of fever, evaluates its therapeutic potential in disease management, and presents recent progress in thermal immunotherapy and the EFT. Furthermore, future perspectives for controllable EFT are discussed and critically assessed, along with its opportunities and main challenges for clinical translation in precision oncology.

This review examines engineered fever therapy (EFT) as a novel cancer treatment, harnessing fever's immunomodulatory effects to enhance systemic immune responses. It explores molecular mechanisms, advances in nanotechnology‐driven thermal immunotherapy, and a bioengineered framework for precise, safe fever induction. The paper evaluates EFT's potential and challenges for clinical translation in precision oncology.