A team of researchers at the University of Louisville discovered that an immune molecule developed for cancer immunotherapy also protected against the future development of multiple types of cancer when administered alone.
The SA-4-1BBL recombinant protein molecule has been used to improve the therapeutic efficacy of cancer vaccines successfully in preclinical animal models. It does this by enhancing the effectiveness of CD8 + T cells, adaptive immune cells formed to target the tumor for destruction. Surprisingly, when the researchers treated SA-4-1BBL alone with healthy normal mice, they were protected when the researchers then exposed them to different types of tumor cells.
"The novelty we report is the ability of this molecule to generate an immune response that patrols the body to detect the presence of rare tumor cells and eliminate cancer before it settles into the body" said Haval Shirwan, Ph.D., professor in UofL's Department of Microbiology and Immunology and at the UofL's Cell Therapy Institute. "As a general rule, the immune system will have to be exposed to the tumor, recognize the tumor as dangerous, and then generate an adaptive and tumor-specific response to eliminate the tumor that it recognizes." Our new finding is so very surprising because system did not see a tumor, so the answer is not to the presence of a tumor. "
The researchers determined that the molecule generates a tumor immune system by activating CD4 + T cells and innate NK cells, thus protecting mice against various types of cancer that they do not have. have never had. This function is an indication of the effectiveness of the molecule in cancer immunoprevention.
In the research published today in Research against cancer, mice never having cancer were treated with SA-4-1BBL alone and then tested at time intervals with tumor cells of cervical cancer and lung. The mice showed significant protection against tumor development, with the greatest protection when tested two weeks after SA-4-1BBL treatment. The cancer prevention effect of cancer generated by SA-4-1BBL lasted more than eight weeks.
"Simply giving SA-4-1BBL alone prevents tumor formation in animal models," Shirwan said. "To our knowledge, this is the first study demonstrating that an immune stimulator, known for its adaptive immunity function, can, as a single agent, activate a mechanism of surveillance of the immune system for protection against various types of tumors. "
Additional tests showed that CD8 + T cells were not needed for protection, but when CD4 + T and NK cells were removed, protection failed, indicating that both types of cells were needed for get the desired effect. The lack of need for CD8 + T cells indicates that the process is not a conventional acquired immunity.
Although the research, which was conducted in collaboration with FasCure Therapeutics, LLC, tested cervical and lung cancer in mice, the protective function of SA-4-1BBL functions without context of specific tumor antigens. which gives it an effective prevention potential. any number of types of tumors.
"We are very excited about the cancer immuno-prevention possibilities offered by this molecule, its effectiveness is not specific to the tumor and, as a natural ligand, it does not cause toxicity, unlike to 4-1BB anti-agonist antibodies, as our data clearly show, it is highly minimized because it activates the innate immune cells, "said Esma Yolcu, Ph.D., associate professor at UofL and co-author of the # 39; study.
Pacemakers and inhibitors of immune checkpoints are major regulators of the immune system and function in the same way as the "brake" and "gasoline" pedals of a vehicle. Cancer eludes the immune system through a variety of means, including immune checkpoint inhibitors, which inhibit the immune response against a tumor. Pacemakers, on the other hand, serve the function of accelerator, improving the immune responses against cancer.
Drugs intended to block the action of immune checkpoint inhibitors have already shown therapeutic efficacy for several types of cancer clinically and are approved by the Food and Drug Administration (FDA). According to Shirwan, the focus is now on the immune boosters of the checkpoints.
"Several antibody molecules are currently undergoing clinical trials for cancer immunotherapy as immune boosters for control points. However, nothing has yet been approved." by the FDA that gives a positive signal to the T cells, "said Shirwan. "Immune control point inhibitors relieve the foot, so to speak, as a stimulator of the immune control point, putting the gas on the immune system to destroy the tumor.
"Another big surprise is that an antibody directed against the same receptor targeted by SA-4-1BBL does not protect against tumors, demonstrating the unique and desired characteristics of SA-4-1BBL for the tumor." immunoprevention of cancer. "
Shirwan and Yolcu plan to conduct further tests on SA-4-1BBL as part of cancer immuno-prevention.
"While the notion of cancer immuno-prevention is attractive, the design of clinical trials presents a challenge to the target population," Shirwan said. "However, with advances in cancer screening technologies and genetic tools to identify high-risk individuals, we hope to eventually be able to test the SA-4-1BBL molecule in immunoprevention in individuals prone to certain cancers, as well as in the presence of precancerous lesions ".
New findings could help oncologists determine effectiveness of checkpoint inhibitors
Research against cancer (2019). DOI: 10.1158 / 0008-5472.CAN-19-2401
University of Louisville
Immunostimulatory molecule effective against cancer (February 15, 2019)
recovered on February 16, 2019
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