56
homologue is present they deliver higher specificity towards the substrate. But as
they are from a non-mammalian source, they elicit immunogenicity, which is the
major disadvantage of these enzymes. A few of them include carboxypeptidase G2,
penicillin G amidase, β-lactamase, cytosine deaminase, etc. (2) Non-mammalian
enzymes (with mammalian homologue); though from a non-mammalian source
they have their counterpart in humans, having a lower level of expression, so that
enzymes administered will have more activity. β–glucuronidase, carboxyantigen
and carboxypeptidase A are some among them. The homologous nature of these
enzymes makes them generate lower immunogenicity. However, their specificity
towards prodrug activation at tumour cells seems reduced. (3) Mammalian enzymes
are also used in prodrug therapy where their mammalian nature eliminates risk of
immunogenicity. But their major disadvantage is prodrug conversion, which may
occur in normal tissues too. Some of the mammalian enzymes are alkaline phosphatase, α-galactosidase, etc (Table 2.2).
2.4
Enzymes as Digestive Aids
Digestive disorders are common, such as malabsorption, lactose intolerance and
celiac disease. Enzyme supplementation is used to manage these digestive disorders
as they are mostly due to lack of digestive enzymes. From the nineteenth century
itself, pancreatic enzyme preparations were used as digestive aids.
Table 2.2 Enzymes for antibody-directed enzyme prodrug therapy (ADEPT), prodrugs and
active cytotoxic drugs
Enzymes
Prodrug
Cytotoxic drug
Potential
Targets
Carboxypeptidase
G2
4-[bis-(2-chloroethyl)-amino]
benzoyl-L-glutamic acid
4-[bis-(2chloroethyl)-amino]
benzoic acid
Colon cancer
Penicillin V amidase Doxorubicin-N-phydroxyphenoxyacetamide
Doxorubicin
Lung
carcinoma
Melphalan-N-phydroxyphenoxyacetamide
Melphalan
Lung
carcinoma
β-lactamase
5-fluorouracil-cephalosporin
5-fluorouracil
Colon cancer
Cytosine deaminase 5-fluorocytocine
5-fluorouracil
Colon cancer
β–glucuronidase,
Doxorubicin –glucuronide
Doxorubicin
Lung
carcinoma
Epirubicin-glucuronide
Epirubicin
Lung
carcinoma
Carboxypeptidase A Methotrexate-alpha-phenylalanine Methotrexate
Lung
carcinoma
Alkaline
phosphatase
Etoposide phosphate
Etoposide
Colon cancer
Mitomycin phosphate
Mitomycin
Colon cancer
S.S. Kumar and S. Abdulhameed
homologue is present they deliver higher specificity towards the substrate. But as
they are from a non-mammalian source, they elicit immunogenicity, which is the
major disadvantage of these enzymes. A few of them include carboxypeptidase G2,
penicillin G amidase, β-lactamase, cytosine deaminase, etc. (2) Non-mammalian
enzymes (with mammalian homologue); though from a non-mammalian source
they have their counterpart in humans, having a lower level of expression, so that
enzymes administered will have more activity. β–glucuronidase, carboxyantigen
and carboxypeptidase A are some among them. The homologous nature of these
enzymes makes them generate lower immunogenicity. However, their specificity
towards prodrug activation at tumour cells seems reduced. (3) Mammalian enzymes
are also used in prodrug therapy where their mammalian nature eliminates risk of
immunogenicity. But their major disadvantage is prodrug conversion, which may
occur in normal tissues too. Some of the mammalian enzymes are alkaline phosphatase, α-galactosidase, etc (Table 2.2).
2.4
Enzymes as Digestive Aids
Digestive disorders are common, such as malabsorption, lactose intolerance and
celiac disease. Enzyme supplementation is used to manage these digestive disorders
as they are mostly due to lack of digestive enzymes. From the nineteenth century
itself, pancreatic enzyme preparations were used as digestive aids.
Table 2.2 Enzymes for antibody-directed enzyme prodrug therapy (ADEPT), prodrugs and
active cytotoxic drugs
Enzymes
Prodrug
Cytotoxic drug
Potential
Targets
Carboxypeptidase
G2
4-[bis-(2-chloroethyl)-amino]
benzoyl-L-glutamic acid
4-[bis-(2chloroethyl)-amino]
benzoic acid
Colon cancer
Penicillin V amidase Doxorubicin-N-phydroxyphenoxyacetamide
Doxorubicin
Lung
carcinoma
Melphalan-N-phydroxyphenoxyacetamide
Melphalan
Lung
carcinoma
β-lactamase
5-fluorouracil-cephalosporin
5-fluorouracil
Colon cancer
Cytosine deaminase 5-fluorocytocine
5-fluorouracil
Colon cancer
β–glucuronidase,
Doxorubicin –glucuronide
Doxorubicin
Lung
carcinoma
Epirubicin-glucuronide
Epirubicin
Lung
carcinoma
Carboxypeptidase A Methotrexate-alpha-phenylalanine Methotrexate
Lung
carcinoma
Alkaline
phosphatase
Etoposide phosphate
Etoposide
Colon cancer
Mitomycin phosphate
Mitomycin
Colon cancer
S.S. Kumar and S. Abdulhameed