KLS-3021 An Oncolytic Viral Therapy For Prostate Cancer Could Soon Reach Clinical Trial Stage

KLS-3021 represents a promising advancement in oncolytic virus therapy, particularly for prostate cancer, where it has shown potential to address unmet needs in early and locally advanced disease. This recombinant vaccinia virus is engineered to selectively infect and lyse tumor cells while delivering a triple payload of therapeutic genes: PH-20 hyaluronidase to degrade the tumor’s extracellular matrix, IL-12 cytokine to activate potent anti-tumor immune responses, and soluble PD-1-Fc to block immune checkpoints that allow cancer cells to evade detection.

In preclinical orthotopic models of prostate cancer using luciferase-labeled PC-3 cells, a single intratumoral injection of KLS-3021 demonstrated profound tumor suppression or complete regression, outperforming weekly docetaxel chemotherapy. This efficacy held in both prostate-confined tumors (non-gross, bioluminescent lesions treated on day 9 post-implantation) and locally invasive models with regional lymph node spread (visible/palpable tumors treated on day 29), where primary tumor treatment also reduced metastatic burden in adjacent nodes.

Mechanistically, KLS-3021 achieves broad intratumoral distribution by breaking down dense stromal barriers via PH-20, enabling deeper viral penetration and immune cell access that is often limited in prostate tumors. The IL-12 payload drives Th1 immune polarization, recruiting cytotoxic T cells and NK cells while shifting macrophages to an M1 pro-inflammatory state; meanwhile, sPD1-Fc neutralizes PD-L1-mediated exhaustion, amplifying sustained anti-tumor immunity. Histological analyses confirmed these effects, revealing extracellular matrix degradation, robust immune infiltration, and hallmarks of immunogenic cell death that turn the tumor microenvironment into an in situ vaccine.

For prostate cancer patients, especially those with low- to intermediate-risk disease (Gleason ≤7) under active surveillance, KLS-3021 offers a minimally invasive local intervention to prevent progression without the morbidity of radical surgery or radiation. Its neoadjuvant potential could shrink tumors prior to definitive therapy, potentially de-escalating treatment intensity and improving quality of life. The therapy’s ability to impact both localized and nodal disease also positions it for exploration in higher-risk settings, where current options like androgen deprivation therapy carry long-term toxicities.

Preclinical safety data showed no significant systemic toxicity, such as weight loss, supporting tolerability in models.

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