Clinical First-in-human Dose Escalation Study Evaluating the Safety and Tolerability of Intranodal Administration of an RNA-based Cancer Vaccine Targeting Two Tumor-associated Antigens in Patients With Advanced Melanoma
RBL001/RBL002 are naked ribonucleic acid (RNA) based recombinant vaccines that were
optimized to induce antigen specific CD8+ and CD4+ T cell responses against malignant
melanoma target antigens.
The Targeted antigens are well characterized antigens in melanoma that have been previously
utilized with excellent safety and proven immunogenicity as vaccine targets in a number of
independent clinical trials.
The overall rationale of the study is to determine safety of the novel RNA based vaccine
approach and determine vaccine target antigen directed immune responses as early biomarkers
for clinical mode of action.
The RBL001/RBL002 vaccine is expected to lead to several effects contributing to its
immunological (therapeutic) effect. First, ultrasound guided administration of naked RNA
drug product into lymph nodes is expected to result in rapid uptake of naked RNA by lymph
node resident professional antigen-presenting cells (APCs). Incorporated RNA is known to
translocate to the cytoplasm leading to its translation by the host ribosome complex into
the respective protein antigens. The recombinant vaccine is optimized for immunogenicity and
enables presentation of diverse antigenic epitopes on both HLA-class I as well as HLA-class
II molecules. Consecutively, antigen-specific CD8+ and CD4+ T cell responses will be
triggered by HLA-peptide complexes on the surface of antigen presenting cells. In addition,
RNA administration will also lead to transient activation (change of surface marker
expression and cytokine secretion) of APCs in the targeted lymph nodes particularly via
signaling of TLR 7 and 8 leading to an adjuvant effect, supporting the induction of
target-specific T cell responses with systemic anti-tumor activity.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of adverse events
Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities
Ugur Sahin, Prof. Dr.