CAR T-Cell Therapy Overcomes Solid Tumor Resistance
- LOS ANGELES, CA - A new approach to CAR T cell therapy, engineered to deliver a dual-action punch against cancer, has shown promising results in preclinical models of...
- What: A novel CAR T cell therapy engineered to release both interleukin 12 (IL-12) and a PD-L1 blocker.
- CAR T cell therapy, which harnesses a patient's own immune system to fight cancer, has revolutionized treatment for blood cancers like lymphoma.
Engineered CAR T Cells Show Promise Against Solid Tumors in Preclinical Trials
LOS ANGELES, CA – A new approach to CAR T cell therapy, engineered to deliver a dual-action punch against cancer, has shown promising results in preclinical models of prostate adn ovarian cancer. Researchers at the USC Norris Comprehensive Cancer Center, in collaboration with City of Hope, have developed CAR T cells that simultaneously boost immune activity and block cancer’s defenses, potentially overcoming a major hurdle in treating solid tumors.
CAR T cell therapy, which harnesses a patient’s own immune system to fight cancer, has revolutionized treatment for blood cancers like lymphoma. However, solid tumors - including those of the prostate, breast, lung, and ovary – have proven much more resistant. These tumors create a opposed environment that suppresses the activity of T cells, the immune cells tasked with destroying cancer.
The USC-City of Hope team tackled this challenge by engineering CAR T cells to produce a fusion protein combining interleukin 12 (IL-12), a potent immune booster, and a programmed death-ligand 1 (PD-L1) blocker, an immune checkpoint inhibitor. this combination allows for a localized attack on the tumor, maximizing effectiveness while minimizing systemic toxicity.
“By designing CAR T cells that release both IL-12 and a PD-L1 blocker as a fusion protein, we can make the treatment safe and also much more effective, even against tumors that usually resist CAR T cell therapy,” explained Dr. Saul Priceman, senior author of the study and associate professor at the Keck School of Medicine of USC.
A Localized Attack: How it Works
The key to this innovation lies in the targeted delivery of IL-12. While IL-12 is known to reactivate T cells and improve the tumor environment, delivering it systemically can cause dangerous side effects. By fusing it with a PD-L1 blocker, the researchers ensured that IL-12 activity was concentrated within the tumor microenvironment. PD-L1 is a protein that cancer cells use to evade the immune system; blocking it allows the CAR T cells to function more effectively.
– drjenniferchen
This research represents a important step forward in addressing the limitations of CAR T cell therapy for solid tumors.the strategy of combining IL-12 and a PD-L1 blocker within a single fusion protein is notably clever, as it addresses both the need to activate T cells and overcome the tumor’s immune suppression mechanisms. The localized delivery is crucial for mitigating the toxicity often associated with systemic IL-12 management. While still in the preclinical stage, these findings offer a promising avenue for future cancer treatments.
Study Findings in Mouse Models:
in mouse models of prostate and ovarian cancer, the modified CAR T cells demonstrated a significant reduction in tumor size without causing widespread toxicity. This suggests the therapy can effectively target and destroy cancer cells while sparing healthy tissues.
Potential Broad Applicability:
While the initial study focused on ovarian and prostate cancer, researchers believe this approach could be applicable to a wide range of solid tumors, including those affecting the gastrointestinal tract and brain.
“We believe this new strategy will provide a productive boost to current CAR T cell therapies and can be applicable to multiple cancer types,” said Dr. john P. Murad, assistant professor of research at the Keck School of Medicine and the study’s first author.
Funding:
The research was jointly funded by the Prostate Cancer Foundation, the Department of Defense, and the National Institutes of Health.
CAR T Cell Therapy: A Swift Overview
| Feature | Description |
|---|---|
| Mechanism | Genetically modifies a patient’s T cells to recognize and destroy cancer cells. |
| Current Use | Primarily used for blood cancers (lymphoma, leukemia). |
| Challenge with Solid Tumors | Tumor microenvironment suppresses T cell activity. |
| New Approach | Engineered CAR T cells release IL-12 and block PD-L1 for localized immune activation. |
| Potential Benefits | Increased efficacy, reduced toxicity compared to