Interleukin-12 subunit alpha mRNA (IL-12 p35 mRNA)

Interleukin-12 subunit alpha (IL-12 p35) mRNA is the messenger RNA transcript that encodes the p35 subunit of the heterodimeric cytokine Interleukin-12 (IL-12). IL-12 is a pivotal coordinator of innate and adaptive immunity, consisting of the p35 subunit (encoded by the IL12A gene) and the p40 subunit (encoded by the IL12B gene), which together promote Th1-type immune responses and activate natural killer (NK) and T cells (UniProt P29459) [1]. Beyond its role in IL-12, the p35 subunit can also associate with the EBI3 subunit to form Interleukin-35 (IL-35), an immunosuppressive cytokine that can facilitate tumor progression (PubMed: 17933928) [2]. In contemporary drug development, IL-12 p35 mRNA is utilized as a therapeutic modality in mRNA-based cancer immunotherapies, such as mRNA-2752 and MEDI1191, which are designed for intratumoral delivery (Moderna, 2024) [3]. These therapies aim to induce local expression of the IL-12 protein within the tumor microenvironment to stimulate a robust anti-tumor response, characterized by increased interferon-gamma production and enhanced cytotoxic lymphocyte activity (ClinicalTrials.gov: NCT03733730) [4]. This localized expression strategy is intended to circumvent the severe systemic toxicities, such as liver damage and cytokine storms, that historically limited the clinical utility of recombinant IL-12 protein (PubMed: 31515461) [5].

Other names

IL12A mRNAInterleukin-12 subunit p35 mRNACytotoxic lymphocyte maturation factor 1 mRNANK cell-stimulating factor chain 1 mRNACLMF p35 mRNA

Exogenous administration of mRNA encoding the IL-12 p35 subunit, typically alongside the p40 subunit, leads to the intracellular translation and secretion of functional IL-12 cytokine. This cytokine binds to the IL-12 receptor on T cells and NK cells, activating the JAK-STAT signaling pathway (specifically STAT4) to promote Th1 differentiation and the production of pro-inflammatory cytokines like interferon-gamma, thereby enhancing anti-tumor immunity.