radiation therapy

Novel radiation therapy zeros in on tough-to-treat cancers

Leading-edge radiotherapies hone in on a marker called CEA, which is often associated with colorectal as well as other cancers

City of Hope scientists have developed a remarkable new antibody with the unremarkable name M5A. It can precisely target the antigen CEA, a marker expressed by many types of cancer. 

The Center for Theranostic Studies has just launched two trials using M5A that may prove to be gamechangers for patients with CEA-positive cancers.

Jeffrey Wong
Jeffrey Wong, M.D.

If you haven’t yet heard of theranostics, it is one of the most exciting new fields in precision medicine.

The word is a combination of “therapeutics” and “diagnostics,” and it uses highly targeted substances — in this case M5A — to increase the accuracy of positron emission tomography (PET) scan imaging and the delivery of treatment.

Jeffrey Y. C. Wong, M.D., professor in the Department of Radiation Oncology and co-director of the Center for Theranostic Studies, explained it more colorfully.

“If we think of cancer as enemy combatants hiding in the jungle at night, PET-guided antibody imaging and antibody-guided radiotherapy are like expert snipers wearing thermal goggles to see all opponents, regardless of where they’re hiding or moving,” he said. “These sharpshooters can then precisely target the enemy for a kill.”

Wong, who is principal investigator on both new trials, filled us in on the details. 

A Trial for Advanced Cancers

In this trial, the “sniper” is the M5A antibody, bound to a powerful radiopharmaceutical called actinium 225, which kills cancer cells by emitting high-energy alpha particles.

“As the treatment travels through the bloodstream, M5A homes in on tumors that express CEA, then actinium 225 destroys them,” Wong said.

'If we think of cancer as enemy combatants hiding in the jungle at night, PET-guided antibody imaging and antibody-guided radiotherapy are like expert snipers wearing thermal goggles to see all opponents.'
Jeffrey Wong, M.D.

There is good evidence that this treatment might be highly effective, as preliminary studies in mice have already shown that actinium 225 can decrease the growth of cancers and increase survival rates.

The treatment is administered on an outpatient basis and consists of just one injection, which takes only a minute or two to infuse. Patients are then monitored weekly for six weeks, and if there is any indication of an anti-cancer effect, they will be eligible for a second treatment cycle. 

Candidates for the trial must be at least 18 years old with advanced CEA-positive colorectal, breast or medullary thyroid cancer, or certain pancreatic, stomach or lung cancers that have not responded to standard therapies. 
It’s a Phase 1, first-in-human trial and will test for safety, side effects and the maximum tolerated dose. Secondarily, it will evaluate the efficacy of the treatment.

A Trial for Rectal Cancer

This trial looks at whether a PET scan using radio-labeled M5A can more accurately identify cancer in the body than standard scans, and it’s based on a recently completed study that showed it worked particularly well for patients with cancer of the rectum.

Candidates for this trial must be over the age of 18, with rectal cancer that has spread to the lymph nodes or nearby tissue, who are scheduled for radiation and chemotherapy treatment followed by surgery. 

During the trial, each patient will get an M5A scan before their radiation treatment and then again before surgery. 

The scan before the radiation treatment will help the radiation oncologist precisely define what areas to treat. Then, after the treatment, a second scan will determine how well the patient responded to radiation therapy. This scan will potentially show the surgeon the exact location of each tumor with greater accuracy than a standard scan, which should enable them to find and remove all of the cancer.

And there’s another potential benefit as well.

“After radiation, these scans sometimes show that the tumors have completely disappeared,” Wong said. “And in the future, we may find that patients with a complete response might not need surgery, allowing them to postpone or avoid the need for a colostomy.”

A Future Trial With M5A

The theranostics team was also involved in a preliminary trial with laboratory mice, featured on the cover of The Journal of Nuclear Medicine last December. In this study, M5A was used to deliver interleukin 2 (IL-2), an immunotherapy, to treat CEA-positive breast and colon cancers.

This study, led by John Shively, Ph.D., professor in the Department of Immunology & Theranostics, and his research team, showed that a combination of M5A and IL-2, combined with standard radiation therapy, had a more powerful effect than either alone.

Preparations for the first clinical trial of this treatment are now underway.

A Center of Excellence

In January, the Center for Theranostic Studies at City of Hope was named a Comprehensive Radiopharmaceutical Center of Excellence by the Society of Nuclear Medicine and Molecular Imaging (SNMMI).

It is the highest level of accreditation awarded by the SNMMI, given in recognition of the center’s highly qualified therapy teams, the reliability and quality of care they provide, and their commitment to research and education.

It’s an award that the center’s co-directors — Wong, Shively, Eileen Smith, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology & Hematopoietic Cell Transplantation, and Anna Wu, Ph.D., chair of the Department of Immunology & Theranostics and the Fouad Kandeel Chair in Diabetes & Metabolism Research — take great pride in.

To learn more about enrolling in either of the M5A trials, call 626-218-2247.