Use

REGRESSIN®-V Vetrepharm Immunostimulant Mycobacterium Cell Wall Fraction Immunostimulant U.S. Vet. Lic. No.: 289 Active Ingredient(s): The mycobacteriaceae have been known for many years to have antitumor activity. REGRESSIN®-V is an emulsion of cell wall fractions which have been modified to reduce their toxic and allergic effect, but retain their antitumor activity. REGRESSIN®-V stimulates the activation of macrophages and thymic lymphocytes which kill tumor cells. REGRESSIN®-V contains procaine hydrochloride 0.2% w/v (which exhibits local analgesic properties) and green tracking dye solution 0.1% w/v (which helps indicate the infiltration of the injected tumor mass or area). Indications: REGRESSIN®-V is recommended for the immunotherapy of equine sarcoid in horses. Although REGRESSIN®-V is administered by intratumoral injection, the response is generalized, and untreated sites frequently undergo regression. Prognosis should be guarded in advanced malignant disease with metastases, as remissions will be less frequent. Remissions cannot be guaranteed as each tumor will vary in its response. Dosage and Administration: REGRESSIN®-V is administered only by intratumoral injection. The entire tumor and a small region of adjacent and underlying tissue must be thoroughly infiltrated using no larger than a 20-gauge needle. Injection without careful infiltration of the tumor may not be effective. It is important to mix the emulsion thoroughly and inject the tumor as quickly as possible because the emulsion may begin to separate soon after mixing. The tumor tissue may be very firm and excessive pressure on the syringe plunger may be required to infiltrate the tumor. The injection may produce pain in some animals; anesthetics or additional analgesics may be used. Dosage varies with tumor size, but 1 mL should be considered a minimum dose. Horses: Equine sarcoid is very responsive to immunotherapy with mycobacterium cell wall fractions.5 Large, pedunculated sarcoids should be debulked by partial excision prior to therapy. REGRESSIN®-V is safe for use in pregnant mares. Treatment should be repeated every one (1) to three (3) weeks. Tumors that fail to respond after four (4) treatments should be considered refractory and therapy discontinued. Ninety-four (94) percent of horses treated were free of tumor two (2) years later. Individual doses range from 1 to 60 mL (average about 10 mL). The average cumulative dose is about 10 mL. Withdrawal Time: Do not use in food producing animals. Contraindication(s): Immunotherapy may not be effective in animals receiving concurrent immunosuppressive therapies. Avoid the use of corticosteroids or ACTH where possible. Precaution(s): Store at 2-7?C in a refrigerator, but do not freeze. The emulsion separates on standing. Resuspend by shaking or rotating the vial between the hands until the emulsion has a homogeneous "milky" appearance. If necessary, REGRESSIN®-V may be heated to 65?C to facilitate suspension. Caution(s): The inflammatory response with edema and malaise occasionally is severe after the initial treatment. Therapy should be discontinued until the reaction has subsided. This product contains procaine hydrochloride and should not be used in performance horses within 96 hours of the event. Warning(s): Do not use in food producing animals. Side Effects: Mild fever, drowsiness and an increased metabolic rate leading to decreased appetite may occur for one to two days following a REGRESSIN®-V injection. These are all normal responses to the release of cytokines. 1,2,3 An elevated body temperature enhances the immune function by stimulating lymphocyte activity, 2 and thus should not be considered an adverse side effect. Local inflammation which is sensitive to the touch occurs fairly often, but it usually is not bothersome to the patient. Necrosis with suppuration may occur in regressing tumors and clients should be informed that the tumor may drain for several weeks. Tumors may be aspirated with a sterile syringe and needle to help prevent drainage. If drainage develops, it often may be stopped by application of astringents such as silver nitrate and styptic powders. References: Available upon request. Presentation: 10 mL vials.

These products are made from bacteria of the genus Mycobacterium. The crude product is called BCG and a cell wall extract (MCWE) is purifed from the BCG to produce these products. MCWE has a number of effects on the immune system. These include:

• enhanced cell mediated immunity
• increases the differentiation and proliferation response of B lymphocytes
• increased phagocytic ability
• increased microbicidal properties
• increased tumor cytotoxic properties

There are several types of MCWE products available for use in horses. Nomagen has been discontinued and is currently not available. Regressin is readily available however:

• Nomagen is manufactured by Fort Dodge Laboratories, Fort Dodge, IA 50501 and recently has become unavailable.
• Regressin-V by Vetrepharm Inc., Ontario, Canada N6E2V6;
• Ribigen, RIBI Immunochem Research Inc., Hamilton, Montana 59840.

There are a number of reports that describe the successful therapy of equine sarcoids with intralesional BCG or MCWE, but MCWE preparations have been found to be safer and more effective. Treatment failures with intralesional MCWE may be encountered in animals with multiple sarcoids. Because MCWE products require macrophages and lymphocytes as effectors, it is possible that treatment failure in cases of multiple sarcoids results from a decrease in the normal functions of antigen recognition or processing and presentation by macrophages.

For more on sarcoids and sarcoid treatment see the article Sarcoids in Horses.