Therapeutic Payloads To Macrophages In A Tumor Specific Manner

As the macrophages playing an important and diverse roles during the cancer progression. However, cancer therapies basing on the macrophage modulation are lacking in tools; that can recognize and deliver therapeutic payloads to macrophages in a tumor specific manner. Macrophages are white blood cells that accumulate in tumors, where they aid cancer progression.

As a result, treatments tending to interfere with normal macrophage functions in healthy organs. We previously identified a macrophage binding peptide. Most tumors contain macrophages, a type of immune cells, that aid tumor growth through a number of mechanisms. Tumor associated macrophages (TAMs) act to stimulate growth of new blood vessels, remodel the extracellular matrix to promote metastasis, and enhance drug resistance.

Macrophages in a tumor

A major barrier to achieve this goal, though, is how to distinguish TAMs from macrophages in normal organs. Delivering drugs to tumors, while avoiding exposure to healthy tissues, is a central goal in cancer treatment; Identifying a cell surface protein specific to only macrophages in tumors and not healthy tissues is an exciting finding with the real possibility of improving the specificity and potency of therapies for a wide range of cancers.

Phage display involves putting thousands of random pieces of DNA into phages, which are viruses that infect and grow in bacteria. The piece of DNA in each phage makes a peptide, a small piece of a protein, that is displayed on the surface of the phage. The result is an extensive library of random peptides on the surface of the phages. The library of phages was then exposed to a macrophage cell line, which led to the identification of a macrophage-binding peptide dubbed CRV.

Tumor’s blood vessels

CRV successfully homed and bound to TAMs in the tumor tissue while avoiding surrounding healthy tissues. To bind the TAMs, CRV had to move from the tumor’s blood vessels into the tumor tissue itself a process called extravasation. The rapid extravasation of CRV to reach TAMs was an extremely encouraging sign; that this peptide has the potential to carry therapeutic cargo into solid tumors. CRV exhibits a higher affinity for tumor macrophages; than for other cells in tumors or for other macrophage types elsewhere in the body.

By these the results demonstrating that study have defining a potentially novel target on TAMs for improving TAM-based cancer therapy; This opens the possibility for a number of therapies that target TAMs; ranging from highly specific delivery of chemotherapy to tumors; to the development of TAM-binding molecules that could potentially reverse TAMs from being tumor promoters to potent anti-tumor weapons.