Quantitative cancer-immunity cycle modeling to optimize bevacizumab and atezolizumab combination therapy for advanced renal cell carcinoma

TL;DR

This study introduces a quantitative model of the cancer-immunity cycle to optimize combination immunotherapy for advanced renal cell carcinoma, integrating biological data and pharmacokinetics for personalized treatment strategies.

Contribution

We developed a novel quantitative cancer-immunity cycle model that predicts tumor evolution and treatment response, aiding in optimizing combination therapy for RCC.

Findings

Identified optimal bevacizumab and atezolizumab treatment regimens.

Calibrated model with clinical immunohistochemistry data.

Proposed tumor biomarkers with predictive clinical value.

Abstract

The incidence of advanced renal cell carcinoma(RCC) has been rising, presenting significant challenges due to the limited efficacy and severe side effects of traditional radiotherapy and chemotherapy. While combination immunotherapies show promise, optimizing treatment strategies remains difficult due to individual heterogeneity. To address this, we developed a Quantitative Cancer-Immunity Cycle (QCIC) model that integrates ordinary differential equations with stochastic modelling to quantitatively characterize and predict tumor evolution in patients with advanced RCC. By systematically integrating quantitative systems pharmacology principles with biological mechanistic knowledge, we constructed a virtual patient cohort and calibrated the model parameters using clinical immunohistochemistry data to ensure biological validity. To enhance predictive performance, we coupled the model with pharmacokinetic equations and defined the Tumor Response Index (TRI) as a quantitative metric of efficacy. Systematic analysis of the QCIC model allowed us to determine an optimal treatment regimen for the combination of bevacizumab and atezolizumab and identify tumor biomarkers with clinical predictive value. This study provides a theoretical framework and methodological support for precision medicine in the treatment of advanced RCC.