Breaking B-Cell Tolerance to Produce Antibodies that Eradicate Leukemias and Lymphomas
Abstract
Targeted immunotherapies are urgently needed for the treatment of life-threatening leukemias and lymphomas. Tumor specific antigens are not universally present on cells and the antigen profiles of tumors change when single antigens are targeted by monoclonal antibodies. Thus, while monoclonal antibodies have proven capacity to eradicate hematolymphoid and solid tumors, tumor specific and tumor associated antigen (TAA) targets are variably immunogenic and animal vaccinations with these antigens do not readily produce therapeutically viable antibodies. Polyreactive anti-tumor antibodies are not produced when peripheral B cell tolerance mechanisms are intact. Our work studying allo-HCT patient samples has now led to improved understanding about how B cell tolerance mechanisms dampen recognition of host/self. Cancer relapse after allo-HCT in patients who never develop chronic graft versus host disease (cGVHD) reveals how host-protective mechanisms dampen responsiveness to tumor. Our primary objective is to develop urgently needed B-cell immunotherapies for the treatment of life-threatening hematolymphoid malignancies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1135283
Entities
People
- Stefanie Sarantopoulos
Organizations
- Duke University