Intratumoral IL-12 Electroporation for Melanoma

The melanoma treatment landscape has changed dramatically during the last 7 years with the approvals of immunotherapy and targeted agents. Intratumoral immunotherapies have not, however, garnered as much attention as their systemic counterparts, but have demonstrated promising results with talimogene laherparepvec (T-VEC), which was approved by the US Food and Drug Administration (FDA) for the treatment of melanoma of the skin and lymph nodes in 2015.¹

Additional intratumoral agents are in the pipeline, including pIL-12, or tavokinogene telsaplasmid, which was granted Orphan Drug Designation by the FDA on June 8, 2017 for the treatment of unresectable metastatic melanoma.²

Intratumoral Therapy

Though advanced melanoma is a systemic disease often treated with systemic therapies, there are merits to administering localized treatment. In addition to visceral metastases, melanoma also frequently demonstrates locoregional progression, which can be painful and disfiguring.

Intratumoral, or intralesional, therapies are injected directly into the tumor and cause lesion regression, but can have systemic effects such that some non-injected lesions demonstrate regression in some patients. T-VEC, for example, has shown efficacy in injected lesions, as well as noninjected regional metastases and, to some extent, visceral metastases.

Intratumoral IL-12 Electroporation: Tavokinogene Telsaplasmid

IL-12 causes an immune response including activation of natural killer and T cells and upregulation of IFN-ɣ, which is targeted to the tumor cells.

Systemic administration of IL-12 is associated with toxicity that limits its use to well-selected patients. IL-12 administered directly into the lesion with electroporation, however, achieves a higher concentration at the tumor without the systemic toxicity.

Electroporation is the key to this route of administration, as it transmits an electrical current through a diode that induces transient pores on the tumor cell membrane, which allows the influx of IL-12 plasmids.

“We inject plasmids directly into the tumor and then gently insert an array of electrodes so that the leads straddle the plasmid injection site. A series of 6 electric pulses is applied. There can be some discomfort, but we’ve seen relatively few side effects between treatments,” Alain Algazi, MD, of the University of California, San Francisco, told Cancer Therapy Advisor.