Chemotherapy of an experimental Trypanosoma cruzi infection with specific immunoglobulin-chlorambucil conjugate.
Hybrid molecules were constructed with either polyclonal antibodies against Trypanosoma cruzi antigens or monoclonal antibody against Trypanosoma brucei brucei low-density lipoprotein (LDL)-receptor conjugated with chlorambucil. Physical-chemical analysis of the hybrid molecule showed four chlorambucil coupling sites in each IgG and a binding constant in the order of 10(4). Maintenance of IgG integrity was indicated by its circular dichroism pattern. Biologic activity of the hybrid molecule was shown by its inhibitory effect on the mobility and proliferation of the parasite. An IgG-chlorambucil conjugate, produced with monoclonal antibody anti-T. b. brucei LDL-receptor, led to the immobilization of the T. cruzi forms, albeit at a much lesser level than that obtained with a mouse polyclonal anti-T. cruzi IgG linked to the drug. Targeting experimental T. cruzi infection with a specific IgG-chlorambucil conjugate resulted in consistent reduction of parasitemia and mortality, thus showing its potential usefulness in controlling the acute form of the disease.
Carvalhaes
M S
MS
Laboratório Multidisciplinar de Pesquisa em Doença de Chagas, Faculdade de Ciências da Saúde, Universidade de Brasília, Brasil.
Santana
J M
JM
Nóbrega
O T
OT
Aragão
J B
JB
Gréllier
P
P
Schrével
J
J
Teixeira
A R
AR
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D014355:Chagas Disease / Q000469:parasitology / Q000473:pathology / Q000628:therapy*; D002699:Chlorambucil / Q000627:therapeutic use*; D018796:Immunoconjugates / Q000378:metabolism / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009068:Movement / Q000502:physiology; D018512:Parasitemia / Q000628:therapy; D011817:Rabbits; D016019:Survival Analysis; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000378:metabolism / Q000502:physiology
D018796:Immunoconjugates; D007074:Immunoglobulin G; D002699:Chlorambucil