title: Regulation of Anti-Tumor Activity Using Monoclonal Antibodies to Alpha-Fetoprotein Receptor and after Immunization with This Protein.
abstract: 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.
authors.affiliation: Moscow Research Institute for Medical Ecology, Moscow Department of Public Health, Moscow, Russia.
authors.forename: Sergey Eu.
authors.initials: SE
authors.lastname: Severin
authors.forename: Alla V.
authors.initials: AV
authors.lastname: Rodina
authors.forename: Mikhail B.
authors.initials: MB
authors.lastname: Nitsvetov
authors.forename: Dmitry V.
authors.initials: DV
authors.lastname: Astahov
authors.forename: Natalia A.
authors.initials: NA
authors.lastname: Kovalenko
authors.forename: Elizaveta Yu.
authors.initials: EY
authors.lastname: Moskaleva
authors.forename: Galina A.
authors.initials: GA
authors.lastname: Posypanova
authors.forename: Olga N.
authors.initials: ON
authors.lastname: Popova
authors.forename: Vladimir K.
authors.initials: VK
authors.lastname: Sologub
authors.forename: Irina A.
authors.initials: IA
authors.lastname: Koromislova
authors.forename: Igor I.
authors.initials: II
authors.lastname: Shmirev
authors.forename: Alexander V.
authors.initials: AV
authors.lastname: Karaulov