Wednesday, June 30, 2021

The Development of FAP-Targeted Cancer

Fibroblast activation protein (FAP) is gaining traction as a clinically useful marker in cancer imaging and treatment. FAP is an enzyme expressed on the surface of cancer-associated fibroblasts, or CAFs, which are found in tumors.

A tumor mass consists of various cellular elements, including malignant cells as well as non-malignant stroma. In solid tumors, such as breast, pancreatic, and colon cancer, more than 90 percent of tumor mass is made of stromal cells. CAFs are among the stromal cells found in the tumor’s microenvironment.

CAFs play an important role in cancer progression. They secrete tumor growth factors that boost tumor size. Additionally, CAFs have an immunosuppressive effect on the body, reducing its innate ability to fight tumor cells. When CAFs are activated, they express unique surface proteins such as FAP. In addition to its presence in tumor cells, high levels of FAP are detected in natural processes such as wound healing and inflammation.

FAP is a critical factor in cancer development. It promotes blood vessel development, also known as angiogenesis, which increases tumor growth, thus resulting in a poor prognosis. Due to its function in tumor progression, FAP makes an excellent target for emerging cancer therapies. Scientists have investigated several FAP-based antitumor therapies such as immunotherapy, vaccines, and antibodies.

Anti-FAP antibodies can be used in cancer radionuclide imaging. For example, SPECT studies show that the iodine-labeled anti-FAP antibody sibrotuzumab accumulates in FAP-positive carcinomas. However, the effect of FAP-based therapies is enhanced when combined with other treatments like chemotherapy.

Clovis Oncology is a biotechnology company developing novel anti-cancer therapies, including radionuclide agents. Based in Boulder, Colorado, Clovis Oncology leads development programs for oncologic treatments targeting specific cancer types.

In June of 2021, Clovis Oncology announced phases 1 and 2 of its LuMIERE clinical trial. The LuMIERE phase 1 trial focuses on the safety and dosing parameters for FAP-2286. Phase 2 evaluates the therapeutic activity of lutetium-labeled FAP-2286 in cancer patients.

Set at the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham, the trial examines the effectiveness of FAP-2286 targeted radionuclide therapy. The LuMIERE study utilizes two different radioactive isotopes. Researchers label FAP-2286 with gallium-68 to test it as an imaging agent in the detection of FAP-positive tumors. In the therapeutic trials, lutetium-177 is attached to FAP-2286. During the product’s preclinical trials, FAP-2286 showed promising effects as an antitumor agent. It successfully damaged CAFs by binding to FAP and causing cell death. Furthermore, after destroying CAFs, FAP-2286 may restore the body’s immune response against cancer.

FAP-2286 is an unlicensed medical product composed of two parts: a FAP-binding peptide and an attachment site for radioactive isotopes. The peptide element binds to FAP on CAFs, whereas the attachment site adds radioactive labeling agents. FAP-2286 is being developed as a theranostic product: depending on the attached radioisotope, it can function as a diagnostic or imaging agent or a therapeutic agent for different types of cancer.

As a peptide-targeted radionuclide therapy (PTRT) product, FAP-2286 works by directly delivering radiation to tumor cells without affecting surrounding healthy tissue. It is the first FAP-targeting PTRT product to enter clinical development.

The Development of FAP-Targeted Cancer

Fibroblast activation protein (FAP) is gaining traction as a clinically useful marker in cancer imaging and treatment. FAP is an enzyme exp...