Xiaofan Li

The Anti-FRα Antibody–Drug Conjugate Luveltamab Tazevibulin Demonstrates Efficacy in Non–Small Cell Lung Cancer Preclinical Models and Induces Immunogenic Cell Death

Abstract Luveltamab tazevibulin is a folate receptor α (FRα)–targeting antibody–drug conjugate currently being evaluated in phase I and II/III clinical trials in endometrial and ovarian cancers (NCT03748186 and NCT05870748), respectively. In this study, we report non–small cell lung cancer (NSCLC) as an additional cancer subtype enriched for FRα expression. In patient-derived xenograft models of NSCLC, FRα-expressing tumors demonstrated robust tumor growth inhibition following luveltamab tazevibulin treatment, demonstrating its potential use for NSCLC treatment. Luveltamab tazevibulin was additionally identified as a potent inducer of immunogenic cell death (ICD). In in vitro cell killing assays, luveltamab tazevibulin induced all three hallmarks of ICD—high mobility group box 1 release, ATP release, and surface exposure of calreticulin. Furthermore, in in vivo vaccination studies, injection of luveltamab tazevibulin–treated tumor cells established protective immunity against subsequent tumor challenge. Consistent with ICD induction, luveltamab tazevibulin treatment in tumor-bearing mice also altered tumor immune cell infiltrate and activation, demonstrating its ability to modulate the tumor immune microenvironment. Given the success of immune checkpoint therapy in NSCLC and luveltamab tazevibulin’s ability to potentiate the immune response, we evaluated the combination therapy of luveltamab tazevibulin with immune checkpoint blockade in syngeneic mouse models and demonstrated that combination treatment results in enhanced efficacy compared with either monotherapy alone. This improved activity with combination therapy was associated with increased tumoral infiltration of CD8+ T cells. In conclusion, the work presented here provides rationale for evaluating luveltamab tazevibulin in NSCLC either as monotherapy or in combination with immune checkpoint blockade.

Risk Prediction Model for Radiation-induced Dermatitis in Patients with Cervical Carcinoma Undergoing Chemoradiotherapy

Radiation-induced dermatitis (RD) is a common side-effect of therapeutic ionizing radiation that can severely affect patient quality of life. This study aimed to develop a risk prediction model for the occurrence of RD in patients with cervical carcinoma undergoing chemoradiotherapy using electronic medical records (EMRs). Using EMRs, the clinical data of patients who underwent simultaneous radiotherapy and chemotherapy at a tertiary cancer hospital between 2017 and 2022 were retrospectively collected, and the patients were divided into two groups: a training group and a validation group. A predictive model was constructed to predict the development of RD in patients who underwent concurrent radiotherapy and chemotherapy for cervical cancer. Finally, the model's efficacy was validated using a receiver operating characteristic curve. The incidence of radiation dermatitis was 89.5% (560/626) in the entire cohort, 88.6% (388/438) in the training group, and 91.5% (172/188) in the experimental group. The nomogram was established based on the following factors: age, the days between the beginning and conclusion of radiotherapy, the serum albumin after chemoradiotherapy, the use of single or multiple drugs for concurrent chemotherapy, and the total dose of afterloading radiotherapy. Internal and external verification indicated that the model had good discriminatory ability. Overall, the model achieved an area under the receiver operating characteristic curve of .66. The risk of RD in patients with cervical carcinoma undergoing chemoradiotherapy is high. A risk prediction model can be developed for RD in cervical carcinoma patients undergoing chemoradiotherapy, based on over 5 years of EMR data from a tertiary cancer hospital.