By blocking malignant cells’ ability to neutralize natural defense antibodies, a new Israeli pharmaceutical is poised to score a touchdown against cancer.
To fight cancer, it sometimes helps to think outside the box, utilizing methods and strategies from other disciplines — like, for example, football.
One football-coaching tactic to prevent the rival team from getting to the goal line is to send out players to run interference, keeping opposing players out of the way so that teammates can run down the field to deliver the ball into the end zone.
Running interference also turns out to be an effective strategy to keep cancer from spreading, says Dr. Michael Schickler, CEO of Yavne-based CureTech. Initially, the body tries to fight the invading cancer cells by developing special defense antibodies known as cytotoxic T-cells.
But cancer is a hardy opponent, and the body’s straightforward defense isn’t always successful. In fact, “Team Cancer” has a few tricks to give it the edge in the battle.
“Recent scientific evidence suggests that many types of cancer now are able to ‘fool’ the T-cells, effectively disabling them,” Schickler tells ISRAEL21c.
The cancerous cells manage to pull off this deception by utilizing a natural “break” of the body’s immune system, producing high levels of a protein called PD-L1, which interacts with a receptor called PD-1 on T-cells. The interaction induces the T-cells to self-destruct. By neutralizing the body’s defenses, cancer cells can spread unchecked.
CureTech has developed an advanced antibody called CT-011, which interferes with a cancer cell’s ability to fool T-cells.
Enabling the body to do its defensive job
“CT-011 links with PD-1 on activated T-cells and blocks its interaction with PD-L1 on the tumor cells, thus preventing the formation of death signals in the T-cells,” says Schickler. The T-cells can then be at their fighting best.
There is even evidence that the body picks up on CT-011′s end-run, developing some additional interference strategies.
“Preclinical as well as clinical evidence suggests that CT-011 may facilitate the formation of specific anti-tumor memory cells that can become active once cancer cells are detected by the immune system,” Schickler says. These unique blood cells fight off future incidences of cancer.
CT-011 was invented by Dr. Brita Hardy and the late Dr. Abraham Novogrodsky of Tel Aviv University. “It belongs to a new class of anti-cancer therapies attempting to harness the body’s immune system against the disease,” says Schickler, who has been involved in the biopharmaceutical business for nearly two decades and has headed CureTech since it was established in 2001. Today, nearly all the company’s 20 employees are researchers working on advancing the capabilities of CT-011.
In 2006, CureTech, which is privately held, made a deal with Israeli pharmaceutical giant Teva Pharmaceutical Industries to conduct research on CT-011. Teva acquired 33 percent of the company at that time. The agreement was upgraded in 2008, with Teva making further investments in the company to fund several Phase II clinical trials.
Recently, CureTech announced preliminary successful results of those trials, involving patients with diffuse large B-cell lymphoma (DLBCL) following stem cell transplantation. After treatment with CT-011, this particularly aggressive form of non-Hodgkin’s lymphoma was halted in 70% of participants of the 72-patient study, compared with 57% in a control group.
Even more strikingly, says Schickler, 84% of patients were alive at the end of the follow-up period, compared with 62% in the historical control. Altogether, more than 400 patients have participated in seven studies with CT-011 to test its effectiveness against colon cancer, multiple myeloma, acute leukemia and pancreatic cancer. CureTech is about to initiate an international Phase II trial for metastatic melanoma, a severe condition with few treatment options.
“It’s an excellent indication of the capabilities of CT-011,” says Schickler, “and I have no doubt that our product will make a major contribution to efforts to fight many types of cancer.”
Following the final results of the study to be completed by the end of this year, CureTech will commence Phase III regulatory studies as a prerequisite for US Food and Drug Administration regulatory approval.