Table 1 Summary of IL-12 gene therapy studies in veterinary medicine

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 dogsPR 3/6 dogs

[57]