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KLS-3021: Innovative oncolytic virotherapy for the treatment of advanced primary and metastatic cutaneous squamous

Kiwon Park¹, Jinwon Seo¹, Sungmin Lee¹

¹Institute of BioInnovation Research, Kolon Life Science, Inc., Seoul 07793, Republic of Korea.

Molecular Therapy. Oncology

|April 20, 2026

Abstract:

Cutaneous squamous cell carcinoma (cSCC) is a highly prevalent malignancy with increasing incidence and limited therapeutic options in advanced or metastatic stages. Patients with high-risk or metastatic cSCC often experience poor outcomes, underscoring the need for novel therapeutic strategies. We investigated the potential of KLS-3021, a recombinant oncolytic vaccinia virus encoding hyaluronidase, interleukin-12, and soluble programmed cell death 1 fused to an Fc domain. KLS-3021 exhibited tumor-selective cytotoxicity and robust replication in cSCC cell lines while sparing normal keratinocytes. In an orthotopic primary cSCC model generated by intradermal injection of A-431 cells, a single intratumoral injection of KLS-3021 induced complete tumor regression. In a metastatic model involving sentinel lymph node lesions, KLS-3021 suppressed tumor progression not only at the primary site but also in metastatic lymph nodes, where viral spread was detected. Histological analyses revealed extensive hyaluronan degradation, viral dissemination, immune cell infiltration, and hallmark features of immunogenic cell death. Similar findings were observed in metastatic lymph nodes, demonstrating viral activity and tumor suppression. Collectively, these results indicate that KLS-3021 exerts potent anti-tumor efficacy in both primary and metastatic cSCC models, supporting its clinical translation as a multifunctional oncolytic virotherapy targeting the physical and immunological barriers of the tumor microenvironment.

Insights

A novel oncolytic vaccinia virus, KLS-3021, effectively eliminated cutaneous squamous cell carcinoma (cSCC) in preclinical models. This therapy demonstrated potent anti-tumor activity against both primary and metastatic cSCC, offering a promising new treatment strategy.

Area of Science:

Oncolytic virotherapy
Cancer immunology
Dermatology

Background:

Cutaneous squamous cell carcinoma (cSCC) presents a significant clinical challenge, particularly in advanced or metastatic stages, with limited effective treatments.
High-risk and metastatic cSCC patients often face poor prognoses, necessitating the development of innovative therapeutic approaches.

Purpose of the Study:

To evaluate the therapeutic potential of KLS-3021, a genetically engineered oncolytic vaccinia virus, against cutaneous squamous cell carcinoma.
To assess KLS-3021's efficacy in both primary and metastatic cSCC models, focusing on tumor regression, viral activity, and immune response.

Main Methods:

KLS-3021, a recombinant vaccinia virus encoding hyaluronidase, IL-12, and PD-1-Fc, was tested in cSCC cell lines and orthotopic mouse models.
Tumor-selective cytotoxicity, viral replication, tumor regression, viral spread, and immune cell infiltration were analyzed post-treatment.

Main Results:

KLS-3021 demonstrated tumor-selective cytotoxicity and robust replication in cSCC cells, sparing normal keratinocytes.
A single intratumoral injection of KLS-3021 led to complete regression of primary cSCC and suppressed progression in metastatic lymph nodes.
Histological analysis confirmed hyaluronan degradation, viral spread, immune cell infiltration, and immunogenic cell death markers in treated tumors and lymph nodes.

Conclusions:

KLS-3021 exhibits significant anti-tumor efficacy against both primary and metastatic cSCC in preclinical models.
KLS-3021 functions as a multifunctional oncolytic virotherapy, overcoming physical and immunological tumor barriers.
These findings support the clinical translation of KLS-3021 for treating advanced cutaneous squamous cell carcinoma.

Read full analysis

Keywords:

MT: Regular Issue cutaneous squamous cell carcinoma hyaluronidase immunogenic cell death interleukin-12 oncolytic vaccinia virus soluble PD1-Fc virotherapy and immunotherapy

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