Document Type

Article

Publication Date

10-3-2019

Publication Title

Clinical Cancer Research: An Official Journal of the American Association for Cancer Research

Pages

37 pp. (Author manuscript)

DOI

10.1158/1078-0432.Ccr-19-0972

Abstract

Purpose: Interleukin-12 (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.

Experimental Design: 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 CD8+ 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 55+ months, respectively). Two cohort A patients (1 with pathologic complete remission) were recurrence-free at 44+ and 75+ months.

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.

Comments

NOTE: This is the author manuscript of a work that will be published in Clinical Cancer Research: An Official Journal of the American Association for Cancer Research.

Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on October 3, 2019; DOI: 10.1158/1078-0432.CCR-19-0972

Original Publication Citation

Bhatia, S., Longino, N. V., Miller, N. J., Kulikauskas, R. M., Iyer, J. G., Ibrani, D., . . . Nghiem, P. (2019). Intratumoral delivery of plasmid interleukin-12 via electroporation leads to regression of injected and non-injected tumors in Merkel cell carcinoma. . Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. DOI: 10.1158/1078-0432.ccr-19-0972.

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