Today's Cancer Research Pioneers
As early as the 1980s, researchers showed that antibodies could provoke the immune system to attack tumors. Compared with monoclonal antibodies, bispecific monoclonal antibodies can bind to two antigens on different cells and link them together. But clinical trials in these first-generation bispecific monoclonal antibodies were disappointing, showing limited efficacy and severe side effects.
In the mid-1990s, Patrick Baeuerle, PhD, honorary professor of immunology at the University of Munich, now at Amgen Research (Munich) GmbH, along with Peter Kufer, MD, a cancer immunologist based in Munich, and colleagues developed a class of novel bispecific monoclonal antibodies called bispecific T-cell engagers (BiTEs) that could potentially overcome these issues. BiTEs are fusion proteins composed of two single-chain antibodies joined by a linker. One antibody targets CD3, an antigen on T cells, and the other targets an antigen on tumor cells.
What's innovative about this design, explained Partow Kebriaei, MD, associate professor in the Department of Stem Cell Transplant and Cellular Therapy at the University of Texas MD Anderson Cancer Center, is that "BiTEs cleverly recruit the tumor to the T cell and then activate the T cell to cause tumor cell lysis. Of note, the tumor cell can be brought to the CD3-positive T cells without regard for T-cell receptor specificity or the need for major histocompatibility complex (MHC) class I molecules for activation."
Blinatumomab (Blincyto™), manufactured by Amgen, is the first BiTE to receive FDA approval. Late last year, the FDA granted blinatumomab breakthrough therapy and orphan product designation for the treatment of non-Hodgkin lymphoma and ALL. The drug targets two antigens—CD3 on T cells and CD19, which is expressed on the surface of B cell-derived ALLs and non-Hodgkin lymphomas—and tethers them together, bringing the T cell directly to the cancer cell. The approval is based on the promising results of a phase 2 open-label trial of blinatumomab in 189 patients with ALL. After two cycles on the drug, about 43% of patients had achieved complete remission or complete remission with partial hematologic recovery.
Currently there are several BiTEs in clinical trials or being constructed, including MT110, which recently completed a phase 1 trial in patients with lung and gastrointestinal cancers.
Activating T Cells: Bispecific T-Cell Engagers (BiTEs)
As early as the 1980s, researchers showed that antibodies could provoke the immune system to attack tumors. Compared with monoclonal antibodies, bispecific monoclonal antibodies can bind to two antigens on different cells and link them together. But clinical trials in these first-generation bispecific monoclonal antibodies were disappointing, showing limited efficacy and severe side effects.
In the mid-1990s, Patrick Baeuerle, PhD, honorary professor of immunology at the University of Munich, now at Amgen Research (Munich) GmbH, along with Peter Kufer, MD, a cancer immunologist based in Munich, and colleagues developed a class of novel bispecific monoclonal antibodies called bispecific T-cell engagers (BiTEs) that could potentially overcome these issues. BiTEs are fusion proteins composed of two single-chain antibodies joined by a linker. One antibody targets CD3, an antigen on T cells, and the other targets an antigen on tumor cells.
What's innovative about this design, explained Partow Kebriaei, MD, associate professor in the Department of Stem Cell Transplant and Cellular Therapy at the University of Texas MD Anderson Cancer Center, is that "BiTEs cleverly recruit the tumor to the T cell and then activate the T cell to cause tumor cell lysis. Of note, the tumor cell can be brought to the CD3-positive T cells without regard for T-cell receptor specificity or the need for major histocompatibility complex (MHC) class I molecules for activation."
Blinatumomab (Blincyto™), manufactured by Amgen, is the first BiTE to receive FDA approval. Late last year, the FDA granted blinatumomab breakthrough therapy and orphan product designation for the treatment of non-Hodgkin lymphoma and ALL. The drug targets two antigens—CD3 on T cells and CD19, which is expressed on the surface of B cell-derived ALLs and non-Hodgkin lymphomas—and tethers them together, bringing the T cell directly to the cancer cell. The approval is based on the promising results of a phase 2 open-label trial of blinatumomab in 189 patients with ALL. After two cycles on the drug, about 43% of patients had achieved complete remission or complete remission with partial hematologic recovery.
Currently there are several BiTEs in clinical trials or being constructed, including MT110, which recently completed a phase 1 trial in patients with lung and gastrointestinal cancers.
SHARE
![Pediatric Supportive Care (PDQ®): Supportive care - Patient Information [NCI]-Overview](https://cdnus.oss-us-west-1.aliyuncs.com/libs/images/NewsJpg/cate_6/072_215x160.jpg)
