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Modified bladder cancer treatment shows promise

SAN ANTONIO, Aug. 23, 2022. A modified tuberculosis vaccine developed at Texas Biomedical Research Institute could help treat a form of bladder cancer, called non-muscle invasive bladder cancer, without strong side effects. Results in mouse models and human cells show promising results and pave the way for human clinical trials. The research, conducted with UT Health San Antonio, was published in the journal Cancer Immunology, Immunotherapy.

"I'm hopeful that with grant or industry support, we can move this right along to clinical trials and explore this treatment for patients who don't have options other than bladder removal," says Robert S. Svatek, MD, a urologic oncologist at the Mays Cancer Center at UT Health San Antonio and co-senior paper author.

Each year in the United States, about 61,700 men and 19,480 women get bladder cancer, and about 17,100 deaths due to the disease occur, according to the American Cancer Society. It is the fourth most common type of cancer in men. About 75% of bladder cancer cases are classified as non-muscle invasive, which means the cancer affects the tissue lining the inner surface of the bladder, but not the bladder muscle.

The Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine was developed for tuberculosis (TB) in the 1920s, and has also been used to treat non-muscle invasive bladder cancer since the late 1970s by stimulating an immune response at the cancer site. It was one of the first cancer immunotherapies and is more effective than chemotherapy for this type of cancer – but up to 84% of patients cannot tolerate the strong side effects and don't complete the three years of BCG treatment. The last option is to remove the bladder, which leads to reduced quality of life.

"Imagine that there's this great drug that works really well, but you're not able to tolerate it," Dr. Svatek says.

Texas Biomed Professor Jordi B. Torrelles, PhD, specializes in TB, and has been working on a modified BCG vaccine for the past six years to improve TB treatment in the lungs. Specifically, Dr. Torrelles and his team remove certain lipids from the cell envelopes of the bacteria in the BCG vaccine. This "delipidated" vaccine still triggers the body to produce well-regulated immune responses, but reduces overzealous inflammation that causes severe tissue damage.

"It is more targeted and allows for a longer, slower response, which makes it more effective," Dr. Torrelles says.

Thanks to a San Antonio Medical Foundation grant, Dr. Torrelles was able to team up with Dr. Svatek and Hong Dixon, PhD, a research scientist specializing in drug development at Southwest Research Institute (SwRI), to test the modified vaccine for bladder cancer.

Dr. Torrelles and his lab made two versions of the delipidated vaccine based on different TB bacteria strains: sub-strain TICE developed in the U.S., and sub-strain Tokyo developed in Japan.

Dr. Svatek's lab conducted the tests in a mouse model of bladder cancer and in cells collected from human cancer patients. Both versions were equally effective compared with the original vaccine at killing cancer, but the modified Tokyo version caused less inflammation and fewer side effects than the TICE version.

"We were not expecting such a clear difference between the strains," says Dr. Torrelles, who has patented the modified vaccine for bladder cancer.

Now, the collaborators plan to seek funding for a phase 1 clinical trial in human patients. "Since this is based on an already FDA-approved treatment, we are hopeful it can proceed in a timely way," Dr. Torrelles says.

SOURCE Texas Biomedical Research Institute

Posted: August 2022

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