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Experimental study of the maternal effects on tumor immunity of infant mice with C1300 mouse neuroblastoma
I Sakamoto1, H Kawakatsu, T Kidowaki
1Department of Pediatrics, Kyoto Prefectural University of Medicine, Japan.
Abstract:
The spontaneous regression of neuroblastoma (NB), one of the most common malignant tumors in childhood, is found to occur in 1% to 2% of patients with NB, especially in young infants. An unexpectedly favorable response to therapy is also noticed in infants suggesting the potential presence of an immune mechanism. Monoclonal C1300-S and C1300A-4 cell lines were established from polyclonal C1300 cells in our laboratory. Adult female A/J mice that had rejected 1 x 10(3) NB cells (C1300S-3) or 1 x 10(5)-10(6) NB cells (C1300A-4) were used as immunized mothers. The immunized mothers with C1300A-4 or C1300S-3 were found to have specific antibodies to C1300S-3 cells by 51Cr release assay of complement dependent cytotoxicity. Newborn mice, 24 hours after birth from immunized or nonimmunized mothers, were inoculated with 1 x 10(3) C1300S-3 NB cells. The same antibody that was assayed in the immunized mothers was detected in this offspring by the antibody-dependent cell cytotoxicity (ADCC). The tumor incidence in the offspring of the immunized mothers was found to be less than that of the offspring of the nonimmunized mothers. This study suggests that the lower tumor incidence in the offspring of immunized mothers compared with offspring of nonimmunized mothers may be attributed to their ADCC activity. Furthermore, the antibody that has the ADCC activity was proven to be immunoglobulin G by a serum absorption test using IgG absorbant. This study offers insight into the relationship between transported mother-infant immunoglobulins and on its potential control of NB.
Insights
Maternal antibodies, specifically immunoglobulin G, may protect infants from neuroblastoma (NB) by activating antibody-dependent cell cytotoxicity (ADCC). This research suggests a potential immune mechanism for controlling childhood NB tumors.
Area of Science:
- Immunology
- Pediatric Oncology
Background:
- Neuroblastoma (NB) is a common childhood cancer with spontaneous regression in some infants.
- Favorable responses to therapy in infants suggest an underlying immune mechanism.
- Specific cell lines (C1300-S, C1300A-4) were derived from NB tumors for experimental use.
Purpose of the Study:
- To investigate the role of maternal antibodies in protecting offspring from neuroblastoma.
- To determine if antibody-dependent cell cytotoxicity (ADCC) plays a role in neuroblastoma regression.
- To identify the type of immunoglobulin involved in this protective immune response.
Main Methods:
- Immunization of adult female A/J mice with neuroblastoma cells.
- Assaying for specific antibodies in immunized mothers using complement-dependent cytotoxicity.
- Inoculating newborn mice from immunized and non-immunized mothers with neuroblastoma cells.
- Measuring antibody-dependent cell cytotoxicity (ADCC) and tumor incidence in offspring.
- Identifying the antibody type using serum absorption tests with immunoglobulin G (IgG) absorbents.
Main Results:
- Immunized mothers developed specific antibodies against neuroblastoma cells.
- Antibodies with ADCC activity were detected in offspring of immunized mothers.
- Offspring of immunized mothers showed a lower tumor incidence compared to controls.
- The antibody mediating ADCC activity was identified as immunoglobulin G (IgG).
Conclusions:
- Maternal immunoglobulin G (IgG) transferred to offspring may confer protection against neuroblastoma.
- Antibody-dependent cell cytotoxicity (ADCC) is a potential mechanism for this protection.
- This study highlights the significance of mother-to-infant immunoglobulin transfer in controlling pediatric neuroblastoma.