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Regulation of Anti-Tumor Activity Using Monoclonal Antibodies to Alpha-Fetoprotein Receptor and after Immunization
Sergey Eu. Severin1, Alla V. Rodina, Mikhail B. Nitsvetov
1Moscow Research Institute for Medical Ecology, Moscow Department of Public Health, Moscow, Russia.
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.
Insights
Monoclonal antibodies targeting the alpha-fetoprotein receptor (AFP-R) show potential in cancer therapy by activating immune responses and inhibiting tumor growth. However, high concentrations may block cytotoxic activity, requiring careful dosage in cancer treatment strategies.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Alpha-fetoprotein receptor (AFP-R) is implicated in oncogenesis.
- Monoclonal antibodies (mAbs) offer targeted therapeutic potential.
- Understanding immune responses to tumor-associated antigens is crucial for cancer therapy.
Purpose of the Study:
- To investigate the effects of mAbs against AFP-R on tumor cell survival and sensitivity.
- To assess AFP-R antibody levels in cancer patients.
- To evaluate the therapeutic potential of AFP-R targeting in preclinical models.
Main Methods:
- In vitro studies using monoclonal antibodies against AFP-R.
- Analysis of serum antibody levels in cancer patients.
- In vivo tumor models in immunized animals.
Main Results:
- Monoclonal antibodies to AFP-R bind to both mouse and human tumor cells.
- Elevated levels of antibodies, particularly IgM, to AFP-R were observed in cancer patients, suggesting an immune response.
- Immunization with AFP-R inhibited tumor growth in a mouse model.
Conclusions:
- Monoclonal antibodies to AFP-R can modulate anti-tumor immunity.
- AFP-R is a potential target for cancer immunotherapy.
- Further research is needed to optimize mAb concentration for effective cancer treatment.