Table 1.
Summary ofIL-12gene therapy studies in veterinary medicine
| No. and type of animals included in the study | Study design | Type of treated tumors | Type of gene delivery | Route of gene delivery | Type of therapeutic IL-12 gene | Treatment outcome | Ref | |
|---|---|---|---|---|---|---|---|---|
| 1 |
16 cats (GFP ± mIL-12) + 13 cats (fIL-12) |
phase I dose escalation study on naturally occurring tumors |
soft tissue sarcomas |
viral delivery (adenovirus controlled by heat-inducible promotor) |
i.tu. |
murine feline |
systemic toxicity at high adenoviral doses high expression of IL-12 in all tumors IFN-γ intratumoral expression detected only with high doses side effects correlated with IFN-γ expression |
[33] |
| 2 |
7 horses |
phase I/II study on naturally occurring tumors |
metastatic melanoma |
direct plasmid injection |
i.tu. |
human |
41% mean reduction of tumor size after single plasmid injection (11/12 treated tumors) CR after 3 plasmid injections in 1/12 tumors only short response (regrowth 11/12 tumors) histological change of treated tumors no side effects |
[46] |
| 3 |
8 horses |
phase II/III placebo-controlled study on naturally occurring tumors |
metastatic melanoma |
direct plasmid injection |
i.tu. |
equine |
regression in tumor size, with mean volume of treated tumors decreasing to approximately 80% of baseline value side effect: local peritumoral oedema of smaller treated lesions |
[48] |
| 4 |
7 horses |
pharmacokinetics study |
metastatic melanoma |
direct plasmid injection |
i.tu. |
equine |
plasmid enters peripheral blood 10 minutes after intratumoral DNA application and is present up to 36 hours post injection, with peak concentration at 30 minutes intratumoral expression of IFN-γ was detectable in all melanoma samples with high interindividual variability |
[47] |
| 5 |
6 dogs |
dose escalating study on experimentally induced tumors |
transmissible venereal tumors |
EGT |
i.tu. |
human |
statistically significant growth delay of treated tumors CR in all of the treated tumors systemic release of IL-12 and/or IFN-γ antitumor effect on distant untreated tumors |
[66] |
| 6 |
8 dogs |
phase I/II study on naturally occurring tumors |
mast cell tumors |
EGT |
i.tu. |
human |
50% median reduction of tumor volumes (ranging from 15 – 83%) systemic release of IL-12 and/or IFN-γ change in histological structure of treated tumors |
[56] |
| 7 |
7 dogs |
phase I feasibility and safety study |
N/A |
EGT |
i.m. |
human |
systemic release of IL-12 (1/6 dogs) induction of IFN-γ response (3/6 dogs) no detectable side effects |
[76] |
| 8 |
6 dogs |
phase I/II study on naturally occurring tumors |
different types of tumors |
EGT |
i.m. |
human |
systemic release of IL-12 and/or IFN/γ in 4/6 animals prolongation of patients' life |
[65] |
| 9 |
N/A |
description of ECGT protocol/case report |
head and neck tumors |
ECGT (IL12 + BLM) |
i.tu. |
N/A |
report on eradication of two tumors (the same two patients are also presented in the study under no. 10) |
[72] |
| 10 | 6 dogs | phase I/II study on naturally occurring tumors | different types of highly malignant tumors | ECGT (IL-12 + BLM) | i.tu. | feline | CR 3/6 dogs PR 3/6 dogs | [57] |
Ref: reference; GFP: green fluorescent protein; mIL-12: murine IL-12; fIL-12: feline IL-12; EGT: electrogene therapy; ECGT: electrochemogene therapy; i.tu. intratumoral; i.m.: intramuscular; BLM: bleomicyn; CR: complete response; PR: partial response.