Prevalence and utility of pharmacokinetic data in preclinical studies of mRNA cancer vaccines

Abstract

In this brief report, we provide insights into current practices in preclinical messenger RNA (mRNA) cancer vaccine characterization. To enable a more automated and thorough survey of mRNA cancer vaccine data in the literature, we implemented natural language processing to mine abstracts from PubMed followed by annotation of the selected articles. Through this analysis we identified a gap in the literature wherein pharmacokinetic (PK) characterization is not reported in mRNA cancer vaccine-focused articles. As a result, the field is unable to evaluate and discuss cross-study PK and pharmacodynamic (PD) relationships nor the translation of these relationships from preclinical species to humans. As the field of mRNA cancer vaccines is rapidly evolving, there is value in expanding our understanding of preclinical PK/PD relationships and how they relate to PK/PD in humans.

FIGURE 1

PK considerations for mRNA cancer vaccines. (a) Following intravenous administration of a monoclonal antibody, the most common modality for cancer immunotherapies, the drug distributes into peripheral tissues from the vasculature. The antibody has its desired effect upon binding to its antigen. This effect may take the form of several different mechanisms, from directly activating a pathway to recruiting innate cells through the Fc domain. In contrast, (b) depicts the path of an mRNA cancer vaccine, which goes through many steps following drug administration to achieve the final effect of activating T cell that will attack the tumor. After administration, the cancer vaccine may remain intact or have some dissociation of the mRNA and carrier, all of which are able to distribute to tissues. Once in the tissue, the vaccine will be taken up by innate immune cells, where the mRNA must be translated into a protein, processed, and finally presented on the surface of antigen presenting cells. This peptide presentation, along with immune stimulation signals, will activate antigen‐specific T cells that are able to attack the tumor. The additional complexity of the mRNA cancer vaccine is highlighted with a gray background for emphasis. mAb, monoclonal antibody; mRNA, messenger RNA; PK, pharmacokinetic. Created with biorender.com.

FIGURE 2

Natural language processing (NLP) framework for mining data from PubMed abstracts and full text articles. Articles were retrieved from PubMed wherein the text mining tool I2E (Linguamatics) and NLP technologies were utilized to identify abstracts that followed our specified inclusion and exclusion criteria. Several removal steps, both automated and manual, followed. Last, manual annotation with our in‐house tool Highlighting Annotation Web Kit (HAWK) was completed on the selected articles by the study team.