Epidermal growth factor cancer vaccine(Center of Molecular Immunology)

Introduction: In Cuba, lung cancer represents the first cause of mortality for both sexes. Non-small cell lung cancer (NSCLC) is the most prevalent histology. Overall, 75-85% of NSCLC overexpress EGFR and its ligands. EGFR overexpression has been implicated in the malignant transformation by promoting cell proliferation and survival. CIMAvax-EGF is a therapeutic vaccine composed of recombinant-human EGF conjugated to a carrier protein and Montanide as an adjuvant. CIMAvax-EGF is intended to induce antibodies against self-EGF that block the EGF-EGFR interaction. Objectives: To characterize the efficacy and safety of CIMAvax-EGF as maintenance in NSCLC patients treated in the real-world setting. Results: 106 patients diagnosed with advanced NSCLC at the National Institute of Oncology and Radiobiology, who had at least stable disease after first-line therapy, were enrolled in the study. The initial four CIMAvax-EGF doses were administered every 2 weeks and then, patients received monthly re-immunizations. Globally, 52.8% of the patients were 65 years or older, 77.4% had an ECOG 1 and 62.3% had an adenocarcinoma. The median survival time (MST) was 14.6 months. Patients younger than 65 years had a MST of 16.7 months and subjects with ECOG 0 survived for 29 months. The median progression-free survival was 8.16 months. Overall, 36.8% and 19.8% of patients maintained disease control at 6 and 12 months, respectively. The most frequent adverse events were pain (27.3%) or induration (7.3%) at the injection site and local erythema (10.9%). Conclusion: CIMAvax-EGF, as an EGF depleting immunotherapy used as switch-maintenance was safe and effective in patients with NSCLC.

This phase I clinical trial is designed to assess the safety and feasibility of the epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR) T-cell generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer (NSCLC) patients. Compared to viral systems, the piggyBac transposon system is a simpler, more economical, and alternative way to introduce chimeric antigen receptor (CAR) transgenes into T cells.

This study recruited nine patients with advanced relapsed/refractory EGFR-positive NSCLC for two cycles of the piggyBac-generated EGFR-CAR T cells at dose of 1 × 10⁶ cells/kg or 3 × 10⁶ cells/kg of body weight. The patients were monitored for adverse events, clinical response, and persistence of plasma GFR-CAR T cells.

Infusions of piggyBac-generated EGFR-CAR T cells were well tolerated in all nine patients. The most common adverse events were grade 1 to 3 fever and there were no patients who experienced grade 4 adverse events or serious cytokine release syndrome. After treatment, eight of nine patients showed detectable EGFR-CAR T cells in their peripheral blood. One patient showed a partial response and lasted for more than 13 months, while six had stable disease, and two had progressed disease. The progression-free survival of these nine patients was 7.13 months (95% CI 2.71-17.10 months), while the median overall survival was 15.63 months (95% CI 8.82-22.03 months).

This Phase I clinical trial revealed that the non-viral piggyBac transposon system-engineered EGFR-CAR T-cell therapy is feasible and safe in treatment of EGFR-positive advanced relapsed/refractory NSCLC patients. Future study will assess it in more patients or even possibly with a higher dose. Trial registration number NCT03182816.