Regulation of Anti-Tumor Activity Using Monoclonal Antibodies to Alpha-Fetoprotein Receptor and after Immunization with This Protein.
The object of this work was to study (i) the effect of monoclonal antibodies (mAb) to a receptor (R) of an oncofetal protein of an alpha-fetoprotein (AFP) on the survival rate and sensitivity of tumor target cells to the cytotoxic action of effector cells, (ii) the level of Ab to AFP-R in the blood serum of patients with malignant tumors (iii) the effect of blood serum with a high level of Ab to AFP-R on the survival rate of tumor cells in vitro, and also (iv) the effect of immunization of animals with an AFP-R preparation on subsequent development of a grafted tumor. It is shown that mAb to AFP-R of clones 2E1, 5C6 and 2B8 effectively bond to both mouse tumor cells and to human tumor cells. Monoclonal Ab to AFP-R of the studied clones do not affect the proliferation of tumor cells of mice and insignificantly inhibit the proliferation of human tumor cells. In patients with malignant tumors, a substantial increase was detected of both the sum Ab to AFP-R, and Ab of the class IgM, and simultaneously an increase of the fraction Ab to AFP-R of the class IgM, which indicates the induction of a primary immune response to AFP-R in such patients. Separate clones of mAb to AFP-R are capable of activating the immune system in respect to tumor cells, inducing of antibody-dependent cellular cytotoxic activity, but with an increase of the concentration of mAb to AFP-R to 1 &mgr;M, the blocking of the cytotoxic activity of peripheral blood mononuclear cells in respect to human tumor cells is possible. In the case of single immunization of mice with an AFP-R preparation, isolated from tumor tissue of lung cancer of a human, inhibition of the growth of a tumor, grafted four days after the immunization, was observed.
Severin
Sergey Eu.
SE
Moscow Research Institute for Medical Ecology, Moscow Department of Public Health, Moscow, Russia.
Rodina
Alla V.
AV
Nitsvetov
Mikhail B.
MB
Astahov
Dmitry V.
DV
Kovalenko
Natalia A.
NA
Moskaleva
Elizaveta Yu.
EY
Posypanova
Galina A.
GA
Popova
Olga N.
ON
Sologub
Vladimir K.
VK
Koromislova
Irina A.
IA
Shmirev
Igor I.
II
Karaulov
Alexander V.
AV