Back to Search
Start Over
Intratumoral Delivery of Plasmid IL12 Via Electroporation Leads to Regression of Injected and Noninjected Tumors in Merkel Cell Carcinoma.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Feb 01; Vol. 26 (3), pp. 598-607. Date of Electronic Publication: 2019 Oct 03. - Publication Year :
- 2020
-
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.<br />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.<br />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 <superscript>+</superscript> 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, respectively.<br />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.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Aged
Aged, 80 and over
CD8-Positive T-Lymphocytes immunology
Carcinoma, Merkel Cell immunology
Carcinoma, Merkel Cell pathology
Cohort Studies
Female
Humans
Interleukin-12 genetics
Interleukin-12 metabolism
Male
Middle Aged
Neoplasm Metastasis
Patient Safety
Pilot Projects
Skin Neoplasms immunology
Skin Neoplasms pathology
Treatment Outcome
Carcinoma, Merkel Cell drug therapy
Electroporation methods
Gene Transfer Techniques
Immunotherapy methods
Interleukin-12 administration & dosage
Plasmids administration & dosage
Skin Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 26
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 31582519
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-19-0972