Intratumoral injection of IL-12 plasmid DNA – results of a phase I/IB clinical trial

Abstract

Effective eradication of established tumor and generation of a lasting systemic immune response are the goals of cancer immunotherapy. The objective of this phase IB study was to assess the safety and toxicity of treatment to metastatic tumor underlying the skin with the DNA encoding interleukin-12 (IL-12). This treatment strategy allowed the patient's own tumor to serve as a source of autologous antigen in the tumor microenvironment. We proposed that IL-12 protein produced by the transfected cells would result in the generation of both a local and systemic antitumor response. The tumor was treated with either three or six intratumoral injections of plasmid containing IL-12 DNA. This treatment strategy resulted in no significant local or systemic toxicity. The treatment did not result in an increase in serum IL-12 protein. The size of the treated lesion decreased significantly (greater than 30%) in five of the 12 patients. However, nontreated subcutaneous lesions or other disease did not decrease in size.

Melanoma Treatment with Intratumoral Electroporation of Tavokinogene Telseplasmid (pIL-12, Tavokinogene Telseplasmid)

“…In a separate Phase 1/1B clinical trial, intralesional IL-12 leads to regression of injected lesions by at least 30% in five of 12 patients treated. However, there was no evidence of clinically meaningful systemic immune activation since regression of nontreated lesions was not observed in any patient [35]. Similar findings have been observed in patients treated with intralesional IL-2, which leads to frequent regressions of treatment lesions but not abscopal regressions of untreated lesions [36,37].…”

New insights into IL-12-mediated tumor suppression

“…delivery of a plasmid encoding IL-12 led to some beneficial clinical effect at the tumor site and even in non-treated lesions. [127][128][129] The treatment seemed however less efficient when IL-12 was delivered encoded by a vector derived from a highly attenuated strain of the canarypox virus. 130 Viral delivery of IL-12 was also used in patients with advanced digestive cancer, but only led to mild antitumor effects.…”

Cancer Electrogene Therapy with Interleukin-12

“…The delivery systems for IL-12 gene therapy are various and include transfer of naked plasmid DNA alone [27,28], adenoviral [29][30][31][32][33] or other viral vectors [34][35][36], as well as gene gun [37,38], electroporation [39][40][41][42] and other non-viral vectors [43,44]. Clinical studies in human and also in veterinary oncology were initiated and the first results showed that IL-12 gene therapy is a safe treatment with some beneficial clinical effect [28,[45][46][47][48][49][50][51][52][53][54][55].…”