Bispecific antibodies retarget murine T cell cytotoxicity against syngeneic breast cancer in vitro and in vivo
Moreno, M. Belen ; Titus, Julie A. ; Cole, Michael S. ; Tso, J. Yun ; Le, Nhat ; Paik, Chang H. ; Bakács, Tibor ; Zacharchuk, Charles M. ; Segal, David M. ; Wunderlich, John R.
Springer
Published 1995
Springer
Published 1995
| ISSN: |
1432-0851
|
|---|---|
| Keywords: |
Key words Bispecific antibody ; Redirected lysis ; Targeted cytotoxicity ; Mammary tumor ; Mouse model
|
| Source: |
Springer Online Journal Archives 1860-2000
|
| Topics: |
Medicine
|
| Notes: |
Abstract Bispecific antibodies with specificity for CD3 and a tumor antigen can redirect cytolytic T cells to kill tumor targets, regardless of their natural specificity. To assess the clinical potential of bispecific antibodies for treatment of human cancers we have, in the present study, adapted a totally syngeneic mouse model to the targeting of mouse T cells against mouse tumors in immunocompetent mice. We show that gp52 of the mouse mammary tumor virus (MTV) can serve as a tumor-specific antigen for redirected cellular cytotoxicity. Chemically crosslinked and genetically engineered bispecific antibodies with specificities for gp52 and murine CD3 ɛ-chain induced activated mouse T cells to specifically lyse mouse mammary tumor cells from cultured lines and primary tumors from C3H-MTV+ mice. Retargeted T cells also blocked the growth of mammary tumors in vitro as well as their growth in syngeneic mice. These findings identify murine MTV-induced mammary adenocarcinomas as a solid-tumor, animal model for retargeting T cells with bispecific antibodies against syngeneic breast cancer.
|
| Type of Medium: |
Electronic Resource
|
| URL: |