Therapeutic biologics

In veterinary and human medicine, novel products are currently being developed to harness nonspecific and select immune responses intended to support treatment of serious, systemic disorders. Although labeled as biologics, these immune therapeutic agents do not act in the same manner as conventional vaccines (also called biologics). Instead, these products are specifically intended to elicit an immune response that may alter the course of the disease (e.g., cancer) or modify the patient’s response to an immunologically mediated disorder (e.g., atopic dermatitis, osteoarthritis).

The following table includes only those products that have been licensed (fully or conditionally) by the U.S. Department of Agriculture and are available in the United States. This information is included in the AAHA Canine Vaccination Guidelines to identify immune therapies licensed for use in dogs. Included is a brief description of indications for use, availability (i.e., some products are only available through specialists, e.g., oncologists), proposed mechanism(s) of action, and general comments. This table is NOT intended to serve as a comprehensive guideline for the administration of any product to an individual patient.

This table will be updated as new products are licensed and become available for use in veterinary medicine.

Condition/Disease (Product Name & Manufacturer)	Canine Oral Melanoma (ONCEPT; Boehringer Ingelheim Vetmedica, Duluth, GA)
Indication for Use	Adjunctive therapy that aids in extending survival times of dogs with stage II or III canine oral melanoma for which local disease control has been achieved (negative local lymph nodes or positive lymph nodes that were surgically removed or irradiated). The vaccine is administered in a 0.4 mL dose volume to dogs via transdermal administration. Initial treatment requires four doses of vaccine administered at 2-wk intervals. Thereafter, the vaccine should be administered at 6-mo intervals. Xenogenic tyrosinase antibody targets tyrosinase on the malignant melanocytes of the affected dog thereby disrupting critical cellular metabolic events (tyrosine pathways) within neoplastic cells. The initial treatment series is 4 doses (1 vial per dose; 0.4 mL/vial) administered by the transdermal route. Inoculation site is medial thigh, caudal to the femur. A single booster dose is administered at 6-mo intervals.
General Comments	The vaccine is comprised of xenogenic (human) plasmid DNA that encodes the gene sequence for Human Tyrosinase (cTyr). The human tyrosinase protein is different enough from the canine tyrosinase protein that it will stimulate an immune response, yet similar enough to canine tyrosinase that the immune response is effective against canine melanoma cells which express tyrosinase. Treatment does not prevent oral melanoma. The vaccine is administered as part of a defined treatment protocol for oral melanoma. Expected outcome of melanoma vaccine therapy includes significantly prolonged survival times. Is available to specialists practicing veterinary oncology.

Condition/Disease (Product Name & Manufacturer)	Canine B-cell Lymphoma (Boehringer Ingleheim Vetmedica, Duluth, GA) Conditionally licensed
Indication for Use	Indicated for the therapeutic immunization of dogs diagnosed with large B-cell lymphoma upon achieving remission following chemotherapy.
General Comments	Trials to demonstrate efficacy of the product are ongoing and will be based upon the extension of time to recurrence in dogs treated with this product.

Condition/Disease (Product Name & Manufacturer)	Canine Atopic Dermatitis Immunotherapeutic (CYTOPOINT™; Zoetis, Parsippany, NJ)
Indication for Use	Is indicated to aid in the reduction of clinical signs (pruritus, skin lesions) associated with atopic dermatitis in dogs of any age. Product is a monoclonal antibody that targets, and neutralizes, interleukin-31 (IL-31), a key protein involved in the induction of pruritus in canine atopic dermatitis. Product is administered by the subcutaneous route at a minimum dose of 2 mg/kg (0.9 mg/lb) every 4 to 8 wk as needed in the individual patient.
General Comments	The product is available to all licensed veterinarians practicing in the United States.

Condition/Disease (Product Name & Manufacturer)	Canine Osteosarcoma Vaccine, Live Listeria Vector (Manufactured by Antelope Valley Bios, Lincoln, NE; Manufactured for Aratana Therapeutics, Inc., Leawood, KS) Conditionally licensed
Indication for Use	For the treatment of osteosarcoma diagnosed in dogs, one year of age or older. This product license is conditional; efficacy and potency have not been fully demonstrated. Prior to each dose, dogs should be pre-treated with the following regimen beginning two hours prior to administration of the product: Place an intravenous catheter in a peripheral vein Start intravenous fluids (balanced crystalloid solution, e.g. Plasma-Lyte^®, Lactated Ringer’s Solution, etc.) at 2-8 ml/kg/hr (1-2 times maintenance rate, based on the patient’s hydration status and other physical exam findings) Administer carprofen at approximately 2.2 mg/kg subcutaneously Administer diphenhydramine at approximately 2 mg/kg intramuscularly Administer an anti-emetic at standard dose and route Reconstitute one vial of the product with the supplied liquid diluent. Mix well. Introduce the entire contents of the reconstituted product into an intravenous bag containing 100 mL sterile intravenous fluid. Immediately administer the contents of the bag by intravenous infusion over approximately 15-30 minutes. Do not mix with other products, except as specified on this label. The primary series consists of three doses administered at 3-4 week intervals.
General Comments	As required by USDA to progress from conditional licensure to full licensure, Aratana is conducting an extended field study in a clinical setting. Initially, the therapeutic is being made available for purchase at approximately two dozen veterinary oncology practice groups across the United States who participate in the study. For more information, please contact Aratana Customer Service at 1-844-ARATANA (1-844-272-8262).

Condition/Disease (Product Name & Manufacturer)	Tumor-derived Immunotherapy for cancer (canine) (VetiVax, Torigen Pharmaceuticals, Inc.; Farmington, CT)
Indication for Use	Autologous treatment of cancer; therapy is patient-centric and utilizes the patient’s own tumor cells to treat solid tumors. Requires 5 g of unfixed tumor tissue be sent to Torigen Pharmaceuticals, Inc. From this, an injectable solution is prepared. A series of subcutaneous injections (volume not specified) are injected into the patient from which the tumor tissue was collected. One injection weekly for 3 wk.
General Comments	The product is administered intravenously into the cephalic or saphenous vein for a period of at least 15 min. Recommended dosage is 0.5 mL/kg administered based on body weight brackets. Brackets of 2–15 kg, 15–30 kg, 30–45 kg, and 45–60 kg receive 1, 2, 3, and 4 vials respectively of 7.5 mL with 2 doses on week 1–4 at a 2–3-day interval followed by 4 doses every other wk. In the field efficacy and safety studies, TACTRESS was not typically used as a monotherapy. This product is available through board-certified veterinary oncologists.

Condition/Disease (Product Name & Manufacturer)	Immunotherapeutic for the treatment of mixed mammary tumor and mammary adenocarcinoma in dogs. (Immunocidin®, NovaVive, Belleville, ON, Canada)
Indication for Use	Is a mycobacterium cell wall fraction immunostimulant for the treatment of canine mixed mammary tumor and mammary adenocarcinoma. Dosage varies with the tumor size (1.0 mL minimum; 10.0 mL maximum). Maximum dose is 1.0 mL of Immunocidin per cubic centimeter of tumor. Doses are administered at 1 to 3-wk intervals.
General Comments	May be administered as a sole treatment or administered in conjunction with surgery and/or chemotherapy. May be administered to dogs with large mass tumors as a means of decreasing the size of the tumor prior to attempting surgical removal.