MIT’s vaccine-enhanced CAR-T therapy destroys solid tumors

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The addition of cancer vaccines may finally unlock CAR-T cell therapy, a revolutionary treatment for blood cancers, against the most common type of cancer, solid tumors.

Treatment: CAR-T cell therapy begins when a doctor extracts a special type of immune system cell, a T cell, from a patient’s blood. Cells are then engineered to display proteins (called “chimeric antigen receptors” or CARs) that attach to proteins called antigens on cancer cells.

When the cells are injected into a patient, CAR binds to cancer cells and T cells help the immune system attack.

Challenge: CARs are designed to bind one specific antigen. For example, a doctor may treat a lymphoma patient with her CAR-T cell therapy that binds to an antigen called “CD19.” This is because this antigen is common and highly specific for that type of blood cancer.

However, researchers have been unable to identify antigens common to solid tumor cells that are not present in healthy cells.

“In principle, this should apply to any solid tumor.”

Darrell Irvine

This is the main reason why the only approved CAR-T cell therapies are all targeting blood cancers. Another problem is that tumors are surrounded by chemicals that block the immune system, blocking the T cells that find them.

Cancer cells may evolve during CAR-T cell therapy and stop displaying the target antigen. This phenomenon, known as ‘antigen loss’, is also problematic in the treatment of hematologic cancers, where disease can persist despite treatment.

what’s new? MIT researchers have now found that a combination of CAR-T cell therapy and a cancer vaccine can kill two types of cancer: glioblastoma, a fast-growing brain tumor, and melanoma, the most serious skin cancer. We have demonstrated how it enhances efficacy in mice with solid tumors.

“In principle, this should apply to solid tumors that have generated CAR-T cells that could potentially target them,” said lead author Darrell Ervin.

Cancer vaccines helped attack tumor cells with CAR-T cell therapy.

background: In 2019, an MIT team treated a mouse model of glioblastoma with CAR-T cell therapy. It targets a mutant form of the EGFR receptor present in many, but not all, glioblastoma cells. A cancer vaccine containing the same antigen was then administered.

The researchers found that this not only helped CAR-T cell therapy attack tumor cells with the EGFR antigen, but also generated more T-cell-targeting cells in the body. other Antigen on glioblastoma cells.

“This vaccine boost appears to drive a process called antigen spreading, in which one’s own immune system cooperates with engineered CAR T cells to target antigens that the CAR T cells target. It rejects tumors that are not all expressing cells,” said Professor Irvine.

up to date: In a new study published in Cell, researchers tested a combination of CAR-T cell therapy and cancer vaccines in mouse models of glioblastoma and melanoma.

Researchers have found that the vaccine appears to cause changes in CAR-T cells, causing them to produce more of a substance called “interferon gamma.” This may stimulate the body’s natural immune system and help it overcome the hostile environment around the tumor.

The researchers also found that when CAR-T cells killed cancer cells, intact T cells in mice learned to: other Antigens on cancer cells were a red flag. They then seek out and attack cancer cells. Them antigen.

These approaches could dramatically increase the number of patients receiving CAR-T cell therapy.

From this new study, the MIT team also found that the efficacy of vaccine-enhanced CAR-T cell therapy is closely linked to the prevalence of target antigens in tumor cells.

For example, if 50% of mouse cancer cells express the target antigen, there is a 25% chance of complete eradication of a rodent tumor. However, if 80% of the cells express the antigen, the probability of eradication increases to 80%.

Future outlook: The MIT team has already licensed the technology for use in research to Boston-based biotech firm Elicio Therapeutics, which is currently preparing the treatment for clinical trials.

Meanwhile, other groups use young T cells, genetically modify them to be more robust, and combine them with cancer-killing viruses to make CAR-T cell therapy a viable option in the treatment of solid tumors. are working to make

Given that solid tumors account for 90% of all adult cancers, any of these approaches, if successful, could dramatically increase the number of patients receiving CAR-T cell therapy, and hopefully The number of patients going into remission after treatment may also increase.

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