Armored CAR T Cells May Help T-Cell Proliferation in GI Microenvironment

Although heterogeneity associated with solid tumors makes them difficult to treat with adoptive cellular therapies, Raed M. Al-Rajabi, MD, professor of Medicine in the Division of Medical Oncology at the University of Kansas Medical Center and lead of the Gastrointestinal (GI) Medical Oncology Group, believes the answer may lie within armored CAR T cells.

In an interview with CancerNetwork®, Al-Rajabi discussed formulating strategies to help enhance T-cell infiltration and reverse T-cell exhaustion within the GI tumor microenvironment. He spoke in the context of a presentation he gave on immune effector cells in GI malignancies at the 2025 Immune Cell Effector Therapy (ICE-T) Congress. He began by suggesting that that there is not a present strategy that is the most effective at accomplishing T-cell infiltration as well as mitigating T-cell exhaustion, citing a relative heterogeneity of solid tumors such as GI malignancies.

To combat this hurdle, he explained that armored CAR T cells, which are resistant to the immunosuppressive tumor microenvironment, could be employed to enhance T-cell penetration and help T cells linger for longer periods. Furthermore, he expressed that administering more than 1 infusion may help replenish T cells in circulation to infiltrate more of the tumor microenvironment. Finally, he stated that research was ongoing, with a focus on exploring numerous mechanisms to bolster efficacy for patients with GI malignancies.

Transcript:

Right now, we do not have a very good answer [regarding effective strategies for enhancing T-cell infiltration or reversing T-cell exhaustion]. That is one of the biggest hurdles in treating solid tumors with adoptive cellular therapy. These cancers have a significant amount of heterogeneity. Some of them produce certain markers that we can target, [and] some of them do not.

One of the biggest hurdles is the tumor microenvironment. There is a lot of interaction between the tumor microenvironment, whether it's cytokines, megakaryocytes, or other full battery cells that that inhibit the tumor response. One of the promising concepts that we are trying to work on [to fix] these hurdles is armored CAR T cells, where they are protected from an immunosuppressive tumor environment. These armored CAR T cells can also produce cytokines that can help the T cells proliferate and prevent exhaustion in the tumor environment.The way we genetically engineer these T cells will hopefully help them linger and work longer.

Unlike hematological malignancies, we are also requiring more than 1 infusion in solid tumors, and that hopefully will also help replenish the constructs in the patient’s systemic circulation to help infiltrate more of the cancer in the tumor microenvironment. There are [many] smart people working on this. There are many mechanisms we can improve on in the microenvironment.

Reference

Al-Rajabi RM. IEC in GI malignancies. Presented at the 2025 Immune Cell Effector Therapy (ICE-T) Congress; September 27-28, 2025. Kansas City, KS