Remarkably, concomitant overexpression of a 3'-UTR-truncated form of p35 promoted tumor growth in vivo and cell proliferation, cell-cycle progression, and cell survival in vitro.
Data from genetic animal models suggest that in contrast to the central role of IL-12 for tumor immune-surveillance, its close relative IL-23 rather promotes tumor growth.
One of them, in which the p40 and p35 form a covalent heterodimer and in which each subunit is fused to a molecule of scFv(L19), displays an excellent tumor targeting performance in vivo, as assessed by quantitative biodistribution analysis, and a potent anti-tumor effect, superior to the one of IL12-scFv(L19)-FLAG.
Reverse transcriptase-polymerase chain reaction analysis of tumor tissue demonstrated peak expression of IL-12 p35 and p40 at 48 h, which persisted up to 7 days.
Notably, retroviral transduction of tumor cells with p35 did not induce drug resistance, as shown by the absence of long-term tumor cell survival or detectable colony formation activity after CPA treatment.