UCLA's breakthrough immune cell therapy targets deadly kidney cancer

Table of Contents

A New Hope for Kidney Cancer Patients

Researchers at UCLA have developed a groundbreaking approach to treating kidney cancer. This innovative therapy, known as AlloCAR70-NKT, uses specially engineered immune cells that can be administered to any patient without the need for customization. Unlike traditional treatments that require personalized cell engineering from each patient’s own blood, AlloCAR70-NKT is ready to use immediately, offering a faster and more efficient solution.

This advancement represents a significant step forward in cancer treatment. Current therapies often involve lengthy processes, high costs, and extensive personalization, which can delay treatment for patients. AlloCAR70-NKT bypasses these challenges by utilizing lab-made cells derived from stem cells. These cells are pre-equipped with tools to fight cancer, making them immediately available for use.

Dr. Lily Wu, a professor at UCLA’s David Geffen School of Medicine, emphasized the potential of this approach. “We successfully turned stem cells into powerful cancer-fighting immune cells that can be ready to use for any patient,” she said. “This approach overcomes the time delays and safety risks of traditional immunotherapies, especially for patients with aggressive, late-stage disease.”

The Need for Better Solutions in Kidney Cancer Treatment

Metastatic renal cell carcinoma, or advanced kidney cancer, is particularly challenging to treat. While new immunotherapy drugs have shown promise, many patients do not respond to these treatments. Others may initially improve but eventually experience a recurrence. The five-year survival rate for this aggressive form of cancer remains low at just 12%.

Kidney cancer often resists traditional treatments due to its ability to create a hostile environment that protects it from immune attacks. This makes it difficult for doctors and scientists to develop lasting cures. In response, researchers at UCLA’s Jonsson Comprehensive Cancer Center and the Broad Stem Cell Research Center have taken a different approach, aiming to outsmart the tumor and its defenses using the body’s own immune tools in a smarter way.

Engineering the Perfect Fighter Cells

The science behind AlloCAR70-NKT is both cutting-edge and practical. Researchers began with stem cells, which have the potential to develop into almost any type of cell in the body. From these, they created immune cells called NKT cells—natural killer T cells known for their strong immune abilities.

These NKT cells were modified with a chimeric antigen receptor (CAR) designed to target CD70, a protein commonly found on kidney cancer cells. By adding the CAR, the cells gained the ability to detect and attack tumors more effectively.

Dr. Lili Yang, another senior researcher on the study, explained the significance of this work. “Our goal was to create an off-the-shelf therapy that persists and works in patients without causing serious immune complications.” Many existing CAR-T therapies have shown success in treating blood cancers but face challenges when targeting solid tumors like kidney cancer.

To overcome these challenges, the team equipped their NKT cells with three key strengths:

• Direct Cancer Cell Killing: The cells were designed to kill cancer cells directly using both the new CAR and their natural NKT receptors. This allowed them to target even tumors with low levels of CD70.
• Weakening the Tumor Environment: The cells were taught to weaken the protective barriers created by cancer, making it easier for immune cells to attack.
• Avoiding Rejection: The therapy was designed to remove certain host immune cells that would typically fight off donor cells, allowing the therapy to last longer in the body while minimizing long-term risks.

“This multi-pronged approach helps them attack both the tumor and its surrounding support system,” said Dr. Arnold Chin, a urology professor and co-senior author of the study. “It makes them a potent, multifunctional and safer option for metastatic kidney cancer.”

Promising Preclinical Results

In laboratory studies using models of kidney cancer, the results were impressive. The engineered cells demonstrated strong anti-cancer activity on multiple levels:

• Direct Tumor Killing: Even tumors with low levels of CD70 were effectively targeted.
• Tumor Microenvironment Manipulation: The cells worked within the tumor’s microenvironment, reprogramming it to allow other immune responses to take effect.
• Reduced Rejection Risk: By clearing out CD70-positive host immune cells, the therapy lowered the chance of being rejected by the body, giving it more time to work.

These effects combined to create a powerful treatment. In preclinical testing, tumors shrank significantly, offering hope for future human trials.

What Comes Next?

The study, published in Cell Reports Medicine, was led by first authors Yan-Ruide Li and Junhui Hu, both scientists at UCLA. The research was supported by grants from several organizations, including the California Institute for Regenerative Medicine and the U.S. Department of Defense’s Kidney Cancer Research Program.

Because AlloCAR70-NKT does not rely on individual patient cells, it could be manufactured at scale, potentially making it more affordable and accessible. This could be especially beneficial for clinics with limited resources for complex cell engineering.

While human trials are needed to confirm the therapy’s safety and effectiveness, the early results represent a major step forward. For patients with metastatic kidney cancer who have exhausted other options, this kind of treatment could offer a new lifeline.

By creating smarter immune cells that act quickly, last longer, and avoid rejection, UCLA’s team may be paving the way for a new era in cancer treatment.