Innovating new T-cell therapies

When the Iowa City man was diagnosed with stage IV esophageal cancer in March 2021, he knew he wanted to do anything he could to have more time with his family and loved ones.

“I’ve had a good life, but then why not keep it going if you can?” said Larson, 73.

After completing difficult bouts of chemotherapy, Larson contacted the UW Health | Carbone Cancer Center to see which clinical trials he could explore.

Larson recently became the first patient in a phase II clinical trial that uses a modified T-cell therapy in the hopes of creating an immune system response to fight cancer. This is also the first time at UW Carbone that T-cell therapy has been used on a solid tumor patient.

Dr. Nataliya Uboha, who is leading this trial, is excited for the new research possibilities opened up by this trial.

“It really is one of the most exciting areas of research in solid tumors,” Uboha said of T-cell therapy. “We have used this type of technology to treat liquid tumors, like lymphomas, leukemias, hematologic malignancies for a while, but these treatments haven’t crossed over into the solid tumor space until the last few years.”

Cancer spreads because tumor cells evade the body’s natural immune response. T-cells are a type of white blood cell that attack abnormal and infected cells. T-cell therapy uses genetically engineered T-cells designed to recognize, bind to, and kill cancer cells.

“The idea of cell therapy treatments is trying to reprogram people’s immune system so that their own cells can attack the cancer cells, and the hope is that this would result in a more long-lasting effect,” Uboha said. “We are hoping that these modified cells will propagate and stick around long enough to continue attacking the cancer cells.”

This form of cellular immunotherapy has been historically difficult to translate to solid tumors for many reasons, including the immunosuppressive nuances of solid tumor microenvironment. However, there have been promising new studies in recent years that are opening more doors.

To coordinate the necessary resources for this trial, Uboha partnered with Dr. Peiman Hematti, director of the Bone Marrow Collection, Apheresis and Clinical Hematopoietic Cell Processing Center at UW Health. The center has long been involved with T-cell therapy in liquid tumors, and Hematti said he was eager to expand their work into solid tumors.

For this trial, Hematti’s team extracted T-cells from Larson that were sent to a pharmaceutical lab for modification. When those new cells were ready, Hematti handled Larson’s infusion personally. The team has also been monitoring Larson’s response to address side effects.

Larson said he has appreciated the attentive and respectful treatment he has received as part of the trial, and he’s hopeful that the treatment will benefit for him.

“I feel lucky to have gotten this far, and I was thrilled to get into this (trial) just so that there was something to try,” Larson said.

Uboha noted that it took a substantial interdisciplinary and collaborative effort to host such a trial, and it paves the way for additional research in that area. She said a new phase I trial using manufactured immune cells for solid-tumor patients is already underway.

Hematti said he and his team want to keep pursing new clinical research collaborations in this area.

“This was one of my proudest moments,” Hematti said of his involvement with Larson’s treatment. “I’ve done work in blood cancer for a long, long time. To use genetically modified T-cells for the first ever solid tumor patient at UW-Madison was a very proud moment for me.”