Marejka H. Shaevitz

IMAX regimen for laboratory safety study in beagle dogs.

Antibodies used in IHC of canine tissues

Locally injected IMAX does not alter systemic cytokine profiles reflecting minimal systemic absorption. Plasma levels of IFN-α, TNF-α, IL-1β, IL-10, CCL2, CCL5, CXCL1, and CXCL10 at 1 hour after subcutaneous or intratumoral injection of IMAX (containing 1 mg 2E′) in healthy and CT26 tumor-bearing BALB/c mice (7–8 weeks). n = 4 mice per group. Data are the mean ± SD. P value was calculated by Sidak multiple comparisons test, following two-way ANOVA.

Locally injected IMAX is retained at the injection site with minimal systemic absorption

Histology of companion dog tumors before and after IMAX treatment. A, Histology of dog RV soft tissue sarcoma. Left, perivascular lymphocytic infiltration (▲). Middle, lack of identifiable tumor cells and marked leukocytic (primarily neutrophils) infiltration with mitotically active giant cells (→). Right, perivascular lymphocytic infiltration (▲) and blue extracellular and intracellular granular materials (inset) located mainly at the tumor periphery. B, Histology of dog SP soft tissue sarcoma. Right, marked intratumoral lymphocytic infiltration (▲). C, Histology of dog CL mammary carcinomas. Ca, caudal mammary gland; Cr, cranial mammary gland. D, Histology of dog BM mammary carcinoma. Right, some areas of the tumor 3 weeks after the second treatment include both malignant epithelial (*) component and malignant mesenchymal component with osteoid (▲), characteristic of carcinosarcoma. Scale bars, 100 μm.

Immunohistochemistry (IHC) of RV soft tissue sarcoma 2 days post IMAX treatment

Biopsy diagnoses for companion dogs.

Tumor response to locally injected IMAX in companion dogs. A,Dog RV soft tissue sarcoma. B,Dog SP soft tissue sarcoma. C,Dog CL mammary tumors. D,Dog BM mammary tumors. Larger symbols indicate the times at which IMAX was administered.

Skin histology of healthy or tumor-bearing mice pre- and post-IMAX treatment (low mag)

IMAX achieves complete tumor regression at a reduced dose (0.004 mg/mm3) in BALB/c mice with CT26 tumor. A, CT26 tumors at 30 to 50 mm3 were treated with IMAX at concentrations of 1, 0.5, 0.2, 0.05, or 0.005 mg 2E′ equivalent or PBS (control) via intratumoral injection (n = 5 per dose). B, Average tumor growth curves (mean with SD) and (C) survival curves of all groups after treatment. P values (numbers in parentheses) were calculated by log-rank (Mantel–Cox) test.