Stanford University develops novel immunotherapy that reprograms tumor cells to activate immune system to fight cancer
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Stanford University develops novel immunotherapy that reprograms tumor cells to activate immune system to fight cancer
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Stanford University develops novel immunotherapy that reprograms tumor cells to activate immune system to fight cancer.
Therapeutic cancer vaccines aim to induce the activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAAs) and eradicating malignant cells.
Recently, a research team proposed a cancer vaccination method that utilizes myeloid reprogramming to directly convert cancer cells into tumor-reprogrammed antigen-presenting cells (TR-APCs).
In a report titled ” Reprogramming Cancer into Antigen Presenting Cells as a Novel Immunotherapy, ” published March 1 in Cancer Discovery , researchers at Stanford University in Medicine seek to alter cancer cells so that they teach the body’s immune system to fight the source of the cells of cancer.
The researchers say the approach could open up a whole new class of treatments for cancer.
Immune response
Some of the most promising cancer treatments use the patient’s own immune system to attack the cancer, usually by suppressing the immune response to the cancer or by teaching the immune system to recognize and attack cancer more forcefully.
T cells, the part of the immune system that recognizes and attacks new pathogens, including viruses, can be trained to recognize specific cancer antigens.
For example, in CAR-T cell therapy, doctors take T cells from a patient, program them to recognize specific cancer antigens, and then return them to the patient. But there are many cancer antigens, and doctors sometimes have to guess which ones will work best.
A better approach would be to train T cells to recognize cancer through processes that more closely mimic those that occur naturally in the body—such as the way vaccines teach the immune system to recognize pathogens.
T cells learn to recognize pathogens thanks to specialized antigen-presenting cells (APCs) that collect pathogen fragments and present them to T cells in a way that tells them “this is what a pathogen looks like – go get it” .
In cancer, a similar situation occurs when APCs collect a variety of antigens that are characteristic of cancer cells.
In this way, instead of being programmed to attack one or a few antigens, T cells are trained to recognize multiple cancer antigens, making them more likely to launch a multi-pronged attack on cancer.
On March 07, researchers are adept at converting one type of cell into another. Dr. Ravi Majeti, the study’s senior author, and his colleagues had a hunch that if they could convert cancer cells into a type of APC called a macrophage, they could naturally teach T cells what to attack .
Because these APCs carried all of the cancer cell’s antigens, they hypothesized that cancer cells reprogrammed into macrophages might stimulate T cells, Majeti said.
Cell transformation
A previous study in Majeti’s lab showed that cells taken from a patient with a type of acute leukemia could be transformed into non-leukemic macrophages that shared many of the properties of APCs.
In the new study, the researchers programmed mouse leukemia cells so that some of them were induced to transform into APCs.
When the cancer vaccine strategy was tested on the immune systems of mice, the cancer was successfully eradicated in the mice.
Other experiments showed that the cells generated by the cancer cells did indeed function as antigen-presenting cells, sensitizing T cells to cancer.
In addition, the immune system has a strong memory, and when the researchers reintroduced cancer into these mice more than 100 days after the initial tumor inoculation, it still produced a robust immune response.
If this approach works for leukemia, will it also work for solid tumors ?
The research team used the same method to test fibrosarcoma, breast and bone cancers in mice.
Transformation of cancer cells from solid tumors was shown to be less efficient, but positive results were still observed. For these three cancers, the generation of tumor-derived APCs significantly improved survival .
Finally, the researchers went back to the original type of acute leukemia. When human leukemia cell-derived APCs were exposed to human T cells from the same patient, the reprogrammed tumor cells could mount a persistent and systemic attack on the cancer.
Researchers imagine that in the future it may be possible to remove tumor cells, convert them into APCs, and return them to patients as therapeutic cancer vaccines.
Ultimately, it may be possible to inject RNA into a patient without first removing the cells, and transform enough cells to activate the immune system to fight cancer.
Although it may seem like science fiction, the researchers say they are intrigued.
References:
https://doi.org/10.1158/2159-8290.CD-21-0502
Stanford University develops novel immunotherapy that reprograms tumor cells to activate immune system to fight cancer.
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