The Evolution of a Promising Cancer Drug - Nine Years in the Making
Cancer treatment, as many patients can attest, can cause unwelcome side effects. One of the major focuses of research undertaken by our Cell Stress Biology Department at Roswell Park is to find ways to reduce these side effects and improve the quality of life for our patients.
The result of one such study, now more than nine years in the making, was the development of the drug CBLB502. This drug holds dual promise because in addition to reducing cancer treatment side effects it also has potential to prevent and slow the growth of cancer cells.
CBLB502 is a pharmacologically optimized derivative of a protein called flagellin. Flagellin makes up the structure of bacterial flagellum, which is the tail-like organ used by bacteria to move through liquid medium. Flagellin is produced by bacteria, such as Salmonella or Escherichia coli (E. coli), naturally residing in our digestive tract.
When injected into the body, flagellin triggers mobilization of natural defense mechanisms, known as innate immune response, normally used to resist bacterial infection like E. Coli or Salmonella.
This response helps to protect normal cells that are sometimes inadvertently impacted during cancer treatment with radiation or some types of chemotherapy, resulting in negative side effects. By incorporating CBLB502 in a patient’s treatment plan to protect the healthy cells, we are hoping to help patients tolerate aggressive forms of treatment, particularly in more advanced cancers.
In addition to its application for cancer treatment, CBLB502 is considered a radiation antidote for mitigation of risk of death from radiation disasters, including nuclear terrorism and nuclear plant accidents.
Our work on discovery of CBLB502 and its efficacy in preclinical models of radiation therapy were published in Science magazine and in the International Journal of Radiation Oncology, Biology and Physics. Most recent insights into the detailed mechanisms of CBLB502 action, done in collaboration with our research partners at Scripps Research Institute and Sanford-Burnham Medical Research Institute, have been published in Science Magazine.
From Preclinical Research to Clinical Study
We were also pleasantly surprised by the discovery of another useful property of this drug. It appeared that when the body responds to CBLB502, it boosts the antitumor immune response, improving its ability to fight cancer cells. Hence, CBLB502 uniquely combines features of both supportive care and direct anticancer drugs.
A Phase 1 Study for CBLB502 is currently underway in patients with advanced disease, led by Alex Adjei, MD, PhD, FACP, Senior Vice President of Clinical Research and Katherine Anne Gioia Chair in Cancer Medicine. The goal is to find the tolerable dose of CBLB502 that can be given to patients without causing severe side effects and to find its effectiveness in treating patients with locally advanced or metastatic solid tumors that cannot be removed surgically. Eventually, through clinical study of CBLB502, we may find that some tumors are more susceptible than others.
We are also doing a study on healthy individuals that will help us approach development of the drug into a radioprotectant for biodefense use.