Authors: Sebastian Dennis-Beron, Future Science Group
Researchers at Duke University (NC, USA) have produced an antibody that targets an innate immune evasion response exhibited by cancer cells. Once the evasion mechanism is inhibited by the antibody, tumor cells are left vulnerable to complement-mediated cell death while healthy cells are unharmed.
The preclinical work, published recently in Cell Reports, builds on an observation made by senior author Edward F Patz (Department of Pharmacology, Duke University) and colleagues – some cancer patient with early-stage lung cancer tumors do not progress to advanced forms of the disease. These patients differ to those with advanced lung cancer as they carry an antibody against complement factor H (CFH).
CFH prevents the accumulation of complement C3b on cell surfaces and thus inhibits degradation of the cellular membrane, preventing cell death. Antibodies against CFH, therefore, prevent inhibition of this important immune response.
To understand how this immune response could be translated into cancer therapy, Patz and team pooled white blood cells from CFH antibody-expressing cancer patients. The antibody genes were then isolated and cloned to produce the specific cancer-targeting antibodies. The resultant antibodies recognized the same region of CFH as the original patient’s immune system, targeting cancerous cells as opposed to healthy cells.
“This is the first completely human-derived antibody developed as an anticancer therapy, which is very different from other immunotherapy approaches,” stated Patz.
In further experiments, these antibodies were tested in various cancer cells lines as well as in vivo in mice models. Not only did th antibody result in tumor cell death, but they also elicited additional adaptive responses when damaged cells released signaling molecules, resulting potentially in an even greater systemic response.
Patz suggests that the additional cellular response may have profound impact on cancer treatment in the future, though adds that further experimentation is required to fully understand it.
“This could represent a whole new approach to treating cancer, and it’s exciting because the antibody selectively kills tumor cells, so we don’t have significant side effects to achieve tumor control,” Patz continued. “We believe we can modulate the immune response and let the body’s own immune system take over to either kill the tumor or keep it from growing.”
Source: Patz Jr EF, Bushley RT, Moody A et al. A Therapeutic Antibody for Cancer, Derived from Single Human B Cells. Cell Reports DOI: 10.1016/j.celrep.2016.04.038 (2016); Duke University Medical Center press release via EurekAlert!