Antibodies have been investigated as specific targeting agents for cancer diagnosis and therapy, to inactivate toxic substances including drugs and also as passive immunotherapy for neoplastic or infectious diseases. In most cases the antibodies were administered systemically by the intravenous route. More recently, however, there has been increasing interest in the oral administration of antibodies for localised treatment of infections or other conditions in the gastrointestinal tract.
The normal physiological handling of ingested proteins is degradation by proteases in the stomach and intestine into small peptides or amino acids which are subsequently absorbed. Proteolytic enzymes involved in the degradation of orally administered immunoglobulins include pepsin, trypsin, chymotrypsin, carboxypeptidase and elastase. These enzymes initially degrade the antibodies to F(ab′)2, Fab and Fc fragments. The F(ab′)2 and Fab fragments, however, retain some of their neutralising activity locally in the gastrointestinal tract. Various approaches are possible to increase the stability of orally administered antibodies against proteolysis, including formulation in liposomes, coating with polymers and genetic engineering of resistant forms.
The clinical application of orally administered antibodies includes the treatment and prevention of gastrointestinal infections caused by enteric pathogens such as rotavirus, Escherichia coli or Vibrio cholerae in susceptible individuals including those with immunodeficiency diseases and patients with bone marrow transplants. There is also a suggestion that such agents may be useful in preventing chemotherapy-induced gastrointestinal mucositis.
Future opportunities for research include the design of oral dosage forms of antibodies which resist proteolysis and can deliver a greater fraction of immunoreactive antibody locally in the gastrointestinal tract for the treatment of infections or perhaps even to allow the absorption of antibodies for the treatment or prevention of systemic conditions.
Adis International Limited Chymotrypsin Bovine Milk Oral Delivery Oral Dosage Form
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Guarino A, Canani RB, Russo S, et al. Oral immunoglobulins for treatment of acute rotaviral gastroenteritis. Pediatrics 1994; 93(1): 12–6PubMedGoogle Scholar
Morelli D, Menard S, Colnaghi MI, et al. Oral administration of anti-doxorubicin monoclonal antibody prevents chemotherapy-induced gastrointestinal toxicity in mice. Cancer Res 1996; 56: 2082–5PubMedGoogle Scholar
Van deGraaff KM. Anatomy and physiology of the gastrointestinal tract. Pediatr Infect Dis J 1986; 5: S11–6CrossRefGoogle Scholar
Britton JR, Koldovsky O. The development of luminal protein digestion: implications for biologically-active dietary polypeptides. J Pediatr Gastroenterol Nutr 1989; 9: 114–61CrossRefGoogle Scholar
Hatta H, Tsuda K, Akachi S, et al. Oral passive immunization effect of anti-human rotavirus IgY and its behaviour against proteolytic enzymes. Biosci Biotechnol Biochem 1993; 57(7): 1077–81PubMedCrossRefGoogle Scholar
Neu J. Functional development of the fetal gastrointestinal tract. Semin Perinatol 1989; 13: 224–35PubMedGoogle Scholar
Madsen JL. Gastrointestinal transit measurements: a scintigraphic method. Dan Med Bull 1994; 41: 398–411PubMedGoogle Scholar
Ritschel WA. Targeting in the gastrointestinal tract: new approaches. Methods Find Exp Clin Pharmacol 1991; 13: 313–36PubMedGoogle Scholar
Fallingborg J, Christensen LA, Ingeman-Nielsen M, et al. Measurement of gastrointestinal pH and regional transit times in normal children. J Pediatr Gastroenterol Nutr 1990; 11: 211–4PubMedCrossRefGoogle Scholar
Alpers DH, Johnson LR, editors. Digestion and absorption of carbohydrates and proteins. In: Physiology of the gastrointestinal tract. New York: Raven Press, 1987: 1469–87Google Scholar
Gardner MG. Intestinal assimilation of intact peptides and proteins from the diet: a neglected field? Biol Rev 1984; 59: 289–331PubMedCrossRefGoogle Scholar
Gardner MLG. Passage of intact peptides across the intestine. Adv Biosci 1987; 65: 99–106Google Scholar
Hilpert H, Brussow H, Mietens C, et al. Use of bovine milk concentrate containing antibody to rotavirus to treat rotavirus gastroenteritis in infants. J Infect Dis 1987; 156(1): 158–66PubMedCrossRefGoogle Scholar
Hatta H, Tsuda K, Sigemitu A, et al. Productivity and some properties of egg yolk antibody (IgY) against human rotavirus compared with rabbit IgG. Biosci Biotechnol Biochem 1993; 57(3): 450–4PubMedCrossRefGoogle Scholar
Shimizu M, Fitzsimmons RC, Nakai S. Anti-Zs. coli immunoglobulin Y isolated from egg yolk of immunized chickens as a potential food ingredient. J Food Sci 1988; 53(5): 1360–6CrossRefGoogle Scholar
Blum PM, Phelps DM, Ank BJ, et al. Survival of oral human immune serum immunoglobulin in the gastrointestinal tract of low birth weight infants. Pediatric Res 1981; 15(9): 1256–60CrossRefGoogle Scholar
Shimizu M, Nagashima H, Sano K, et al. Molecular stability of chicken and rabbit immunoglobulin G. Biosci Biotechnol Biochem 1992; 56(2): 270–4PubMedCrossRefGoogle Scholar
Eibl MM, Wolf HM, Furnkranz H, et al. Prevention of necrotizing enterocolitis in low-birth weight infants by IgA-IgG feeding. N Engl J Med 1988; 319(1): 1–7PubMedCrossRefGoogle Scholar
Zinkernagel RM. The digestion of colostral bovine immunoglobulins in infants. Experientia 1972; 28: 741CrossRefGoogle Scholar
Losonsky G, Johnson JP, Winkelstein JA, et al. Oral administration of human serum immunoglobulin in immunodeficient patients with viral gastroenteritis: a pharmacokinetic and functional analysis. J Clin Invest 1985; 76(6): 2362–7PubMedCrossRefGoogle Scholar
Roos N, Mahe S, Benamouzig R, et al. 15N-labeled immunoglobulins from bovine colostrum are partially resistant to digestion in human intestine. J Nutr 1995; 125(5): 1238–44PubMedGoogle Scholar
Martin MG, Wu SV, Ohning G, et al. Parenterally or enterally administered anti-somatostatin antibody induces increased gastrin in suckling rats. Am J Physiol 1994; 266 (3 Pt 1): G417–24PubMedGoogle Scholar
Shimizu M, Miwa Y, Hashimoto K, et al. Encapsulation of chicken egg yolk immunoglobulin G (IgY) by liposomes. Biosci Biotechnol Biochem 1993; 57(9): 1445–9PubMedCrossRefGoogle Scholar
Shimizu M, Nakane Y. Encapsulation of biologically active proteins in a multiple emulsion. Biosci Biotechnol Biochem 1995; 59(3): 492–6PubMedCrossRefGoogle Scholar
Cornes J. Number, size, and distribution of Peyer’s Patches in the human small intestine: II. The effect of aging on Peyer’s Patches. Gut 1965; 6: 230CrossRefGoogle Scholar
Heizer WD, Laster L. Peptide hydrolase activities of the mucosa of human small intestine. J Clin Invest 1969; 48: 210–28PubMedCrossRefGoogle Scholar
Hammarstrom L, Gardulf A, Hammarstrom V, et al. Systemic and topical immunoglobulin treatment in immunocom-promised patients. Immunol Rev 1994; 139: 43–70PubMedCrossRefGoogle Scholar
Hilpert H, Gerber H, Amster H, et al. Bovine milk immunoglobulins (Ig), their possible utilization in industrially prepared infants’ milk formula. In: Hambraeus L, Hanson LA, McFarl-ane H, editors. Proceedings of a symposium of the Swedish Medical Research Council. Stockholm: Almqvist and Wiksell International, 1977: 182–96Google Scholar
Mietens A, Keinhorst H, Hilpert H, et al. Treatment of infantile E. coli gastroenteritis with specific bovine anti-E. coli milk immunoglobulins. Eur J Pediatr 1979; 132: 239PubMedCrossRefGoogle Scholar
Nord J, Ma P, DiJohn D, et al. Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients. AIDS 1990; 4: 581–4PubMedCrossRefGoogle Scholar
Ungar BLP, Ward DJ, Fayer R, et al. Cessation of cryptosporidium-associated diarrhea in an acquired immunodeficiency syndrome patient after treatment with hyperimmune bovine colostrum. Gastroenterology 1990; 98: 486–9PubMedGoogle Scholar
Copelan EA, Avalos BR, Kapoor N, et al. Alternate applications of immunoglobulin following bone marrow transplantation. Semin Hematol 1992; 29 (3 Suppl. 2): 96–9PubMedGoogle Scholar
Copelan EA, Bechtel TP, Klein JP, et al. Controlled trial of orally administered immunoglobulin following bone marrow transplantation. Bone Marrow Transplant 1994; 13(1): 87–91PubMedGoogle Scholar
Hollwarth ME, Schuber P, Pfleger A, et al. Necrotising enterocolitis: results of surgery. Pediatr Surg Int 1992; 7: 421–7Google Scholar
Kanto WP, Wilson R, Ricketts RR. Management and outcome of NEC. Clin Pediatr 1985; 24: 79–82CrossRefGoogle Scholar
Wolf HM, Eibl MM. The anti-inflammatory effect of an oral immunoglobulin (IgA-IgG) preparation and its possible relevance for the prevention of necrotizing enterocolitis. Acta Pediatr 1994; 396 Suppl.: 37–40CrossRefGoogle Scholar
Chabner B A, Myers CE. Antitumour antibiotics. In: De Vita VT, Hellman S, Rosenberg SA, editors. Cancer principles and practice of oncology. Philadelphia: Lippincott, 1993: 374–84Google Scholar
Bernhisel-Broadbent J, Yolken RH, Sampson HA. Allergenicity of orally administered immunoglobulin preparation in food-allergic children. Pediatrics 1991; 87: 208–14PubMedGoogle Scholar