Revolutionary CRISPR Method Advancing Personalized Cancer Therapy
- Tamilarasan.S
- Apr 19, 2023
- 2 min read
Solid tumors are more complicated than blood cancers as they are not only induced by genetic mutants in cancer cells but also regulated by the surrounding microenvironment. Studies show that the tumor microenvironment(TME) also initiates cancer and promotes the growth of the tumor. Due to this, various problems are faced in curing these cancers. Anticancer drugs used to kill cancer cells in tumor cells have to spread throughout the tumor vasculature, cross vessel walls, and traverse the tumor tissue. But, the intake of many drugs within the tumor results in heterogeneous conditions, by which an uneven spread of drugs takes place and only the potentially exposed side of the drug react on cancer cells. So the effectiveness of the cytotoxic agent is misdirected.
Even though engineered T-cells called CART-cells are approved for various cancers, they can only act on the proteins exposed in surrounding cancer. But these proteins are not found in solid tumors. In addition, solid tumors are caused in different parts of the body like bones, muscles, and various organs. So they need highly engineered T-cells for the treatment on other hand the solid tumors provide physical barriers for T-cells by suppressing the immune response and using up the local supply of nutrients to fuel their rapid growth
Researchers have shown a novel way of CRISPR gene editing to alter immune cells to target specific mutated proteins for a specific tumor. T-cell receptors (TCRs) enable to specify mutations in the cancer cells. Researchers have used this concept and approached CRISPR-Cas9 non-viral precision genome editing in TCR by knockout and insertion of genes isolated from the patients.
The approach was tested in 16 volunteers with solid tumors, including in the breast and colon. They first isolated the immune cells from the patient's RBCs and sequenced them, here a total of 175 newly isolated cancer-specific immune receptors were found. A neoantigen -specific TCR is a type of T cell receptor that is designed to recognize specific mutations or changes in surface protein expression on cancer cells.
By CRISPR editing, they knocked out the TCR , TRAC & TRBC. The the cells were inserted with neoantigen-specific TCR which were isolated from the immune cells of the patients by one step CRISPR editing.
Three such preparations of gene-edited immune cells were injected back into the patients, for a total of 37 immune receptors were infused into the patients in research. By tumor biopsy, it was identified that the gene-edited immune cells(neoTCR transgenic T cells) were frequently higher near the tumor cells. After one month of treatment, it was identified that the growth of tumors have stopped growing in 5 patients. Two patients had side effects from chemotherapy like fever and chills, which both recovered promptly. Post-infusion biopsies of the patients showed that the genetically engineered cells were found in around 20% of the immune cells in cancer.
Researchers conclude that future advancements in engineered T-cells by removing the immunosuppressive receptors or modifying the metabolism so that they can easily find an energy source to reach the tumor environment may pay way increasing the potential of the T-cells.
References:
Comments