Immunogenicity and Safety Profile of Two Adjuvanted-PD-L1-Based Vaccine Candidates in Mice, Rats, Rabbits, and...

The therapeutic blockade of the PD1/PD-L1 axis with monoclonal antibodies has led to a breakthrough in cancer treatment, as it plays a key role in the immune evasion of tumors. Nevertheless, treating patients with cancer with vaccines that stimulate a targeted immune response is another attractive approach for which few side effects have been observed in combination immunotherapy clinical trials. In this sense, our group has recently developed a therapeutic cancer vaccine candidate called PKPD-L1^Vac which contains as an antigen the extracellular domain of human PD-L1 fused to a 47 amino-terminal, part of the LpdA gene of N. meningitides, which is produced in E. coli. The investigation of potential toxicities associated with PD-L1 blockade by a new therapy in preclinical studies is critical to optimizing the efficacy and safety of that new therapy.

Here, we describe immunogenicity and preliminary safety studies in mice, rats, rabbits, and non-human primates that make use of a 200 μg dose of PKPD-L1 in combination with VSSPs or alum phosphate to contribute to the assessment of potential adverse events that are relevant to the future clinical development program of this novel candidate.

The administration of PKPD-L1^Vac to the four species at the doses studied was immunogenic and did not result in behavioral, clinical, hematological, or serum biochemical changes.

Therefore, PKPD-L1^Vac could be considered suitable for further complex toxicological studies and the way for its clinical evaluation in humans has been opened.