Injecting a redesigned immunotherapy drug directly into a cancer tumor triggered response in metastatic tumors

Injecting a redesigned immunotherapy drug directly into the primary tumor produced an immune response to cancer that had spread to other parts of the body (Image credit – WIX AI)

CANCER DIGEST – March 21, 2026 – In a small clinical trial, patients with a variety of solid tumors saw cancerous tumors that a had spread to other parts of their bodies shrink when the primary tumor was injected with a re-engineered antibody immunotherapy. The results of the trial were published last fall in the journal Cancer Cell.

Led by Jeffrey Ravetech, M.D., Ph.D at Rockefeller University, and Juan C. Osorio, MD, at Memorial Sloan Kettering, the research team re-engineered an antibody immunotherapy that targets a protein receptor called CD-40 that is known to trigger immune attacks on cancer when an immunotherapy drug binds to it. However, patients treated with immunotherapy targeting CD-40 have met with mixed success, often with toxic side effects because CD-40 receptors are present on healthy cells throughout the body.

The researchers at Rockefeller University, however, re-designed the immunotherapy to bind more strongly with a specific part of the CD-40 receptor by improving how the drug interacts with the Fc receptor. In the lab the research team found that targeting the Fc receptor more specifically made the antibody 10 times more effective in triggering an immune response. In addition, in experiments in mice, the research team found that directly injecting the antibody into the tumor resulted in milder side effects.

With that experience, the researchers launched a phase I clinical trial involving 12 patients with several types of tumors that had spread to other parts of the body. Phase I trials are designed primarily to evaluate safety in a small number of patients. Patients had melanoma, kidney cancer and different forms of breast cancer that had spread to other parts of their bodies. 

Following injection of the re-engineered immunotherapy directly into the patients' primary tumors, six of the patients tumors shrank throughout the body, and two patients, one with melanoma and one with breast cancer experienced complete response, meaning their cancers disappeared throughout their bodies. Just as importantly, none of the patients experienced the toxic side effects that had marked other CD-40 targeted immunotherapies.

"The melanoma patient had dozens of metastatic tumors on her leg and foot, and we injected just one tumor up on her thigh," Ravetch said in a press release. "After multiple injections of that one tumor, all the other tumors disappeared. The same thing happened in the patient with metastatic breast cancer, who also had tumors in her skin, liver, and lung. And even though we only injected the skin tumor, we saw all the tumors disappear."

The promising results were enough to allow the team to launch additional clinical trials in collaboration with investigators at Memorial Sloan Kettering and Duke University to further evaluate the therapy. The current phase I and phase II have expanded to nearly 200 patients with bladder cancer, prostate cancer and a form of brain cancer called glioblastoma.

The researchers hope that these trials will help determine what immune system characteristics in different patients determine which patients will benefit most from the treatment.