Colon Cancer Immunotherapy Successful in Small Trial

Targeting the KRAS mutation was found successful in a patient with metastatic colorectal cancer.

Researchers from the National Cancer Institute recently discovered a novel method for targeting the carcinogenic protein created by a mutated form of the KRAS gene.

This finding was made during a study evaluating an immunotherapy for colorectal cancer, which included only 1 patient. When researchers targeted the cancer-causing protein, the patient experienced cancer regression, according to a press release from the National Institutes of Health (NIH).

More than 30% of cancers are the result of mutations in the RAS genes, which includes KRAS, NRAS, and HRAS. Approximately 95% of all pancreatic cancers and 45% of all colorectal cancers are thought to be driven by mutations in the KRAS gene.

The most common mutation, G12D, causes over 50,000 new cases of cancer in the United States each year, according to the NIH. Due to the prevalence of the RAS mutations in multiple cancers, efforts to target this gene are being explored by many institutions, but none have been successful thus far.

In the current study, published by the New England Journal of Medicine, the team of researchers isolated tumor infiltrating lymphocytes that target the G12D mutation from tumor nodules in the lungs after the patient’s colorectal cancer metastasized.

The tumor-infiltrating lymphocytes (TILs) were then grown in the laboratory and infused into the patient intravenously. Investigators discovered that all 7 metastatic nodules regressed after the infusion.

The regression was seen for 9 months, at which time 1 of the lesions progressed and had to be removed. Upon examining this lesion, researchers found that the lesion lost a segment of chromosome 6, which includes the important HLA-C*0802 gene, according to the study.

HCLA-C*0802 is involved with antigen presentation, which is a process where the antigen created by the cell is recognized by the immune system by “presenting” itself on the surface. If the antigen is recognized as foreign, the immune system will fight it.

In this specific case, since there was a lost segment of chromosome 6, the immune system did not recognize the cancer cells as foreign, and did not attack. However, because the lesion was surgically removed, the patient has been in remission for 8 months.

Since this a proof-of-principle study, the researchers said they need to further develop this method to see if this approach could potentially be effective in other patients.

“This study demonstrates for the first time, that this method of administering TILs, called adoptive T cell transfer immunotherapy, can mediate effective antitumor immune responses against cancers that express the KRAS G12D mutation,” Dr Rosenberg concluded. “We have also identified multiple T cell receptors that recognize this KRAS product, thus opening the possibility of T cell receptor gene therapy against multiple types of cancer that express this common mutation.”