Now, a recent study by researchers at the University of North Carolina Healthcare Lineberger Comprehensive Cancer Center has shown that the use of natural killer T (NKT) cells represents a new approach to immunotherapy, producing significant antitumor activity in clinical models of solid tumors.
Gianpietro Dotti, professor of microbiology and immunology at the University of North Carolina School of Medicine, and co-leader of the center’s immunology research program, explained that CAR-NKT cells rely on a multimodal approach, combining direct killing of cancer cells, reprogramming the tumor environment and enhancing systemic immune responses. Which contributes to creating a more immune-responsive environment in tumors.
Doughty noted that CAR-T cells are very powerful, but they face inhibitors in the tumor environment.
The research team found that tumor-associated macrophages inhibit the effectiveness of CAR-T cells, while CAR-NKT cells are able to evade these inhibitory effects by targeting them directly.
Previous research has demonstrated that the ability of CAR-T cells to penetrate and function within solid tumors is restricted, as a result of physical barriers and the suppressive nature of the environment surrounding the tumor.
But CAR-NKT cells, with their unique properties, can recognize glycolipid antigens (they are part of the innate immune response and help activate immune cells such as natural killer T cells (NKT) to be able to recognize infected or abnormal cells, such as cancer cells). Which enhances its ability to combat solid tumors. They can also eliminate M2-like macrophages, which promote tumor growth and suppress immune responses.
The results indicated that CAR-NKT cells also promote the proliferation of the phenotype, meaning they activate T-cell responses against new targets.
“This dual function represents a critical advance in improving CAR-based therapies for solid tumors,” said Shen Zhu, the paper’s first author.
The researchers were also able to help CAR-NKT cells overcome therapeutic exhaustion, a known problem with CAR-T therapies that have been exposed for long periods to tumor antigens. Combining CAR-NKT cells with a PD1 inhibitor (used in cancer treatment) also increased the effectiveness of anti-tumor activity.
Doty noted that his team is focused on developing methods to simplify the process of producing CAR-NKT cells.
He explained: “CAR-NKT cells have been used safely in clinical trials, but manufacturing them for clinical use is more complex than manufacturing CAR-T cells. “We are working to simplify these processes.”
The study results were published in the journal Nature Cancer.
Source: Medical Express
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Lineberger Cancer Center
Breaking News in Cancer Treatment: CAR-NKT Cells Show Promise in Immunotherapy
A groundbreaking study from the University of North Carolina Healthcare Lineberger Comprehensive Cancer Center has shed light on the potential of natural killer T (NKT) cells in cancer treatment. Researchers have found that CAR-NKT cells, a type of immunotherapy, exhibit significant antitumor activity in clinical models of solid tumors. This new approach holds promise in overcoming the limitations of existing treatments, such as CAR-T cells.
According to Gianpietro Dotti, co-leader of the center’s immunology research program, CAR-NKT cells employ a multimodal approach, combining direct killing of cancer cells, reprogramming the tumor environment, and enhancing systemic immune responses [[1]]. This synergistic effect creates a more immune-responsive environment in tumors, paving the way for more effective treatment.
While CAR-T cells have shown remarkable success in cancer treatment, they often face inhibitors in the tumor environment. Specifically, tumor-associated macrophages have been found to hamper the effectiveness of CAR-T cells [[1]]. In contrast, CAR-NKT cells have demonstrated the ability to evade these inhibitors, making them a more promising candidate for cancer treatment.
Recent studies have corroborated these findings. A study published in Nature Communications demonstrated that CAR-NKT cells exhibit superior antitumor activity in vivo compared to CAR-T cells, despite similar antitumor effects in vitro [[2]]. Another study published in the Journal of the American Society for Transplantation and Cellular Therapy showed that off-the-shelf CD19-specific CAR-NKT cells are well-tolerated and can mediate objective responses in relapsed or refractory non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL) patients, even at low doses [[3]].
Moreover, a study published in Molecular Therapy demonstrated that allorejection-resistant CAR-NKT cells can be engineered to exhibit potent antitumor efficacy against blood cancers and solid tumors, both in vitro and in vivo [[3]].
These findings collectively suggest that CAR-NKT cells represent a new and exciting approach to immunotherapy. Their ability to evade tumor-associated macrophages and create a more immune-responsive environment makes them a promising candidate for overcoming the limitations of existing treatments.
As the field of immunotherapy continues to evolve, the study of CAR-NKT cells holds great promise for patients with cancer. Further research is needed to fully harness their potential, but the prospects for improved treatment outcomes are undeniably exciting.
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