Maternal immunization impairs lymphoma growth and CNS/ocular metastasis in the offspring
Ori Braitbard1,2, Allan Bar-Sinai1, Jacob Hochman1
1Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem, Israel.
Abstract:
Maternal immunization is an important tool directed against a variety of infectious maladies in the offspring. A complementary, but less explored area is the use of maternal immunization in the prevention and treatment of childhood cancers. This in part stems from the lack of adequate experimental model systems. Lymphomas of the Central Nervous System (CNS) and ocular involvement pose a therapeutic challenge. Ocular lymphoma is a lethal disease caused mainly by two clinically distinct forms of non-Hodgkin's lymphoma: non-Hodgkin's lymphoma of the central nervous system, or Primary CNS lymphoma (PCNSL), and systemic lymphoma metastatic to the eye. Previously, we developed an experimental model whereby mouse lymphoma cell variants, derived from the S49 T-cell lymphoma, metastasized to the CNS and eyes following Intraperitoneal inoculation at days 7-10 postnatal. Here, we extended the model to study whether maternal immunization can impede CNS/Ocular metastasis in the offspring exposed to the metastatic lymphoma cells. To that effect, female Balb/C mice were vaccinated with either immunogenic, live, S49 lymphoma cell variants, or with a purified protein antigen: the 98 amino acid signal peptide of the envelop precursor protein of Mouse Mammary Tumor Virus (MMTV) endogenously harbored by the S49 lymphoma. The offspring from both vaccination protocols were immunized against a challenge with the CNS/Ocular metastatic lymphoma cells. Immunity was conferred via milk suckling and was prolonged without further challenge for an extended period of at least 3 months. The abovementioned findings constitute a novel experimental model system whereby CNS/Ocular metastasis of malignant lymphoma in the offspring is impeded through maternal vaccination/immunization and thus, can be followed mechanistically as well as for novel therapeutic modalities.
Insights
Maternal immunization can prevent offspring from developing CNS/ocular lymphoma. This study shows that vaccinating mothers protects their young from lymphoma metastasis through milk transfer, offering a new therapeutic avenue.
Area of Science:
- Immunology
- Oncology
- Pediatric Cancer Research
Background:
- Maternal immunization is crucial for offspring health, but its role in preventing childhood cancers is under-explored.
- Central Nervous System (CNS) and ocular lymphomas are challenging pediatric cancers.
- Existing experimental models for studying CNS/ocular lymphoma metastasis are limited.
Purpose of the Study:
- To establish and utilize a novel experimental model to investigate the efficacy of maternal immunization in preventing CNS/ocular lymphoma metastasis in offspring.
- To determine if maternal vaccination can confer immunity against lymphoma cell challenge in neonates.
Main Methods:
- Developed a mouse model where S49 T-cell lymphoma variants metastasize to the CNS and eyes post-neonatal inoculation.
- Vaccinated female Balb/C mice with live S49 lymphoma cells or a purified Mouse Mammary Tumor Virus (MMTV) envelop protein.
- Assessed the transfer of immunity to offspring via milk suckling and its duration.
Main Results:
- Offspring born to vaccinated mothers demonstrated immunity against CNS/ocular lymphoma cell challenge.
- Immunity was successfully transferred through maternal milk.
- The protective effect persisted for at least 3 months without further immunization.
Conclusions:
- Maternal immunization is a viable strategy to impede CNS/ocular lymphoma metastasis in offspring.
- This study presents a novel model for mechanistic investigation and development of therapeutic strategies against pediatric lymphomas.
- Passive immunity transfer via lactation offers a promising approach for childhood cancer prevention.
