Intratumoral delivery of plasmid IL12 via electroporation leads to regression of injected and noninjected tumors in Merkel cell carcinoma

Shailender Bhatia, Natalie V. Longino, Natalie J. Miller, Rima Kulikauskas, Jayasri G. Iyer, Dafina Ibrani, Astrid Blom, David R. Byrd, Upendra Parvathaneni, Christopher G. Twitty, Jean S. Campbell, Mai H. Le, Sharron Gargosky, Robert H. Pierce, Richard Heller, Adil I. Daud, Paul Nghiem

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Purpose: IL12 promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer. Patients and Methods: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. Patients with metastatic MCC (cohort B, N = 12) received up to four cycles total, administered at least 6 weeks apart. Serial tumor and blood samples were collected. Results: All patients successfully completed at least one cycle with transient, mild (grades 1 and 2) AEs and without significant systemic toxicity. Sustained (day 22) intratumoral expression of IL12 protein was observed along with local inflammation and increased tumor-specific CD8þ T-cell infiltration, which led to systemic immunologic and clinical responses. The overall response rate was 25% (3/12) in cohort B, with 2 patients experiencing durable clinical benefit (16 and 55þ months, respectively). Two cohort A patients (1 with pathologic complete remission) were recurrence-free at 44þ and 75þ months, respectively. Conclusions: I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer.

Original languageEnglish (US)
Pages (from-to)598-607
Number of pages10
JournalClinical Cancer Research
Volume26
Issue number3
DOIs
StatePublished - Feb 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine

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