Engineering Bispecific Antibodies That Target ERBB-2 on Breast Cancer Cells
Abstract
The ultimate goal of this project is to develop immunotherapeutic agents that target a patient's own T cells against their cancer. The project took two directions to accomplish this goal: the development of novel single-chain bispecific antibodies and new animal models that more closely resemble human cancers. Although the project has seen some changes in the original plans (such as the focus on a different tumor antigen, the folate receptor), significant progress was made in understanding the effects of this class of immunotherapeutics. In addition, we have developed and now focus on two animal models that provide realistic, albeit challenging, opportunities to evaluate such agents. Our primary findings are that: (1) small, bispecific antibodies with conjugated folate can target folate-receptor-positive tumor cells, both in vitro and in vivo; (2) growth of established transplanted human tumors in TCR/RAG(-/-) mice and endogneous brain tumors in SV40-transgenic mice can be slowed but could not be cured with bispecific conjugates alone; T cell infiltration into the tumors can be achieved but this infiltration needs to be sustained, and (3) CD28 agonists and CTLA-4 antagonists can be used to sustain T cell activity and an anti-CTLA-4 single-chain antibody was engineered for this purpose.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA378096
Entities
People
- David M. Krantz
Organizations
- University of Illinois Urbana–Champaign