Previously, we set up a clinical study in lung cancer patients and are currently acquiring the last follow-up data of all treated patients. In this study, patients undergoing surgery with curative intent (stage I and II), were treated with increasing dose of autologous dendritic cells (DCs) electroporated with patient-specific in vitro transcribed RNA (IVT-RNA) encoding 4-6 neoantigens. These neoantigens were selected based on information obtained from the excised tumor: identification of clonal somatic mutations (whole exome sequencing, WES), expression of the mutation by the tumor (RNAseq and mass-spectrometry, MS), and binding of the mutated peptides to one of the Major Histocompatibility Complex (MHC) class I alleles of the tumor.

This study was successful: preliminary results obtained in the six treated patients displayed no severe toxicities (primary end point) and showed neoantigen specific immunization in 5/6 patients analyzed (secondary end point) and acceptable feasibility (secondary end point) as we were able to treat 6/11 patients recruited in this particular patient population. Time from surgery to treatment, turnaround time (TAT), however, was 5-8 months.

As most lung cancer patients present themselves in stage III and IV and as prognosis of this patient population is dismal even when treated with current available immunotherapy using immune checkpoint inhibitors (ICI), we plan to set-up a follow up clinical trial for these inoperable patients. However, to be able to do that in this patient population, we need to find a workable alternative source of tumor material. In addition, we need to reduce the TAT, the time required for the design and production of the personalized vaccine

In this research project, we have the following two objectives:

Define and validate the nature and quantity of patient material required for the identification of the neoepitopes. A major concern here will be the acquisition of suitable material with minimal discomfort for the patient. In other words, we will acquire all necessary material as part of the diagnostic workout and staging procedure. No extra interventions.

Optimize the timeline for vaccine design and production. In our previous study, vaccine design and production took 5-8 months. Here, we will set up and validate a production process which a TAT of 9 weeks. This short TAT on the one hand and standard chemotherapy/immunotherapy course initiated at diagnosis on the other hand, should ensure that most patient will be able to receive the vaccine doses at the start of consolidation/add-on treatment

Therapeutic vaccinations for patient-specific neoantigens are considered an attractive adjunct to immune checkpoint inhibitors (ICIs) for lung cancer. If clinical trials can show efficacy, these therapeutic approaches will become state of the art treatment. We believe therefore that this study is of general importance as it may significantly improve outcome as well as have a beneficial effect on patient comfort.