Targeting tumor cells with bispecific antibodies and T cells

D. M. Kranz, T. C. Manning, L. A. Rund, B. K. Cho, M. M. Gruber, E. J. Roy

Research output: Contribution to journalArticle

Abstract

It has been known for some time that mammalian immune systems are capable of eliminating large tumor burdens. Redirecting the immune response of a patient to an established tumor has now become the focus of various therapeutic strategies. In this report, two projects toward this goal are described. The first project involves the development of a transgenic mouse model for T cell directed therapeutics. These mice express specific T cell receptor α and β transgenes on a background in which the recombinational- activating-gene-1 (RAG) has been knocked out. The mice express cytotoxic T cells but not either T helper cells or B cells. Despite these deficiencies, the animals are capable of eliminating tumors that express the appropriate peptide/major histocompatibility complex ligand that is recognized by the αβ transgenic T cell receptor. Human tumors grow as transplants in these mice, thereby allowing various agents that redirect the endogenous T cells against human tumors to be tested. The second project involves a description of such agents: bispecific antibodies that simultaneously bind to an immune effector cell and a tumor cell. The bispecific antibody described here consists of folate attached to anti-T cell receptor antibodies, or their fragments. A single-chain Fv coupled with folate can redirect the lysis of human tumor cells that bear the high affinity folate receptor. Preliminary in vivo data showed that the folate/antibody conjugates were also capable of mediating rejection of the human tumor. This transgenic mouse model should now allow the evaluation and optimization of bispecific agents that can redirect a patient's own T cell response.

Original languageEnglish (US)
Pages (from-to)77-84
Number of pages8
JournalJournal of Controlled Release
Volume53
Issue number1-3
DOIs
StatePublished - Apr 30 1998

Keywords

  • Bispecific Antibodies
  • Cytotoxic T Lymphocytes
  • Folate Receptor
  • Transgenic Mice

ASJC Scopus subject areas

  • Pharmaceutical Science

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