Jeannette Kelly1, Megan Padget1, Chad Johannes2, Aleksandar Masic3

1Veterinary Cancer Care, Santa Fe, New Mexico, USA

2Iowa State University, Ames, Iowa, USA

3NovaVive Inc, Belleville, Ontario, Canada

Mycobacterium Cell Wall Fraction (MCWF) is a non-specific immunomodulator derived from a non-pathogenic mycobacterium, Mycobacterium phlei currently licensed in Canada and USA for treatment of mixed mammary tumors and mammary adenocarcinoma in dogs marketed as Immunocidin®. MCWF has been used for treatment of other malignancies such as osteosarcoma, transitional cell carcinoma, soft tissue sarcoma, hemangiosarcoma and transitional venereal tumors in dogs. MCWF is considered a bifunctional anticancer agent that induces apoptosis in cancer cells and stimulates cytokine and chemokine synthesis by immune system cells.

The purpose of the present research was to assess clinical and safety profile of Immunocidin® following multiple intravenous administrations in cats and dogs with various malignancies. In addition, we explored Immunocidin® immunomodulatory potential and effectiveness as an adjunct treatment to oncology standard of care for treatment of various neoplasias in dogs and cats.

Prior to the start of the study, the experimental protocol was reviewed and approved by institutional animal care and use committee. The study was single site-specific, non-blinded, clinical pilot-study conducted at oncology referral clinic Veterinary Cancer Care, Santa Fe, New Mexico, USA. Inclusion criteria for the study were: life expectancy of a minimum of 6 weeks, confirmed neoplasia by histology or cytology and no concurrent radiation or steroid therapy. Total of 35 patients were enrolled in the study. Patients enrolled in the study had the following tumor types: mast cell tumor (1 canine), thyroid carcinoma (1 canine), high grade soft tissue sarcoma (3 canines), lymphoma (8 canines/ 2 felines), fibrosarcoma (1 canine), osteosarcoma (2 canines), injection site sarcoma (1 feline), oral melanoma (2 canines), anal gland adenocarcinoma ( 2 canines), transitional cell carcinoma (1 canine), hemangiosarcoma (4 canines) , mammary adenocarcinoma (3 canines), histiocytic sarcoma (2 canines), pulmonary carcinoma (1 canine), multiple myeloma (1 canine) and pheochromocytoma (1 canine). Immunocicin® (MCWF emulsion) was supplied by NovaVive INC., Canada.

Each vial of MCWF contained 2.5ml at a concentration of 1mg/mL. Dosages administered followed the ranges of: 5kg = 0.1ml; 5-10kg = 0.2-0.25ml; 5-15kg= 0.3ml; 15-25kg= 0.5ml; 25-35kg= 0.75ml; >35kg= 1ml. Prior to administration, each dose was diluted into 150ml sterile 0.9% NaCl and administered intravenously over 30 minutes. Treatments were performed either weekly or every other week depending on standard chemotherapy protocols. The anal glad carcinoma patients were treated every 3 weeks in combination with their Carboplatin treatments. Each patient was also pre-treated with diphenhydramine. Both dogs and cats were treated in this study using the same administration protocol. Each administration was performed on the same day following standard chemotherapy dosing of one of the following: Vincristine (0.5mg/m2), Doxorubicin (27mg/m2), Dacarbazine (800mg/m2) or Carboplatin (225mg/m2) according to standard treatment protocols.

Following administration of MCWF, all animals were closely monitored for 2h in the clinic before being sent home with the owner. Temperature, blood pressure, heart and respiratory rate were assessed every 30-45 min. In addition, whole blood samples were taken every two to four weeks and complete blood counts and clinical chemistry analysis were performed.

Adverse events (AE’s) were observed in 5 animals and were considered minimal. Observed AE’s  included mild lethargy (8) and mild transient hyperthermia (3) observed in some patients within hours after MCWF administration but resolved within 12-24 hours. One canine patient had hyperthermia (104.2 F) and vomiting which resolved within 12 hours with diphenhydramine and Cerenia ® (maropitant citrate) but did require prednisone. No clinically relevant hematology changes were observed. MCWF was used in combination with standard chemotherapy protocols in several cases (injection site sarcoma, histiocytic sarcoma, osteosarcoma) with measurable pulmonary metastasis which remained stable or showed regression radiographically.

Current observations on Immunocidin® safety following intravenous administration and clinical impression in cats and dogs with various neoplasisas are satisfactory and provide a solid base for future research. Additional, controlled clinical studies are planned to further demonstrate Immunocidin® efficacy as conjunctive therapy to standard of care in treatment of hemangiosarcoma and soft tissue sarcoma.

Overall, present data showed that in our clinical setting the MCWF has immunomodulatory potential that can play a role in treating additional neoplasias beyond mammary tumors as an adjunct treatment in combination with standard protocols

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