“A new cellular immunotherapy could be effective in the treatment of metastatic solid tumors”. This was announced by the American National Institutes of Health (NIH), which published in ‘Nature Medicine’ “the first results of a small clinical study in patients with colorectal cancer who had previously undergone multiple therapies” without success: “Personalized immunotherapy shrunk tumors in some patients and was able to prevent their regrowth for up to 7 months”. The approach developed by scientists from the National Cancer Institute (NCI) of the NIH is a personalized approach that consists of genetically engineering the patient’s healthy lymphocytes so that they express specific receptors, capable of recognizing and attacking tumor cells.
So far, different versions of cellular immunotherapy have been shown to be effective against some blood cancers and metastatic melanoma, the NIH says. However, there is still no cellular therapy that works against solid tumors. “The fact that we were able to reverse a metastatic solid cancer proves that the new cellular immunotherapy strategy is promising,” says Steven A. Rosenberg of the NCI’s Center for Cancer Research (CCR), who co-led the research with CCR surgeon Maria Parkhurst. “However, it is important to understand that these results are preliminary,” he says, “and that the new approach needs to be further refined and tested on more types of solid tumors.”
The new approach, the NIH emphasize, overcomes two major challenges in cellular immunotherapy: how to produce large numbers of T lymphocytes capable of specifically recognizing tumor cells; how to increase the ability of the modified T cells to multiply once reinfused into the patient.
For each patient involved in the study, the NIH explain, Rosenberg and colleagues collected lymphocytes present in the tumor. On these lymphocytes, through sophisticated molecular characterization techniques, they identified and isolated the receptors that recognized specific changes in the tumor of each patient. After having genetically sequenced them, using a retrovirus they inserted the genes of these receptors into healthy lymphocytes collected from the circulating blood of each patient. The genetically modified lymphocytes were then multiplied in the laboratory, obtaining hundreds of millions, and reinfused into the patients where they expressed the T cell receptors specific to the tumor and continued to multiply. “By taking the natural receptors present in a very small number of T lymphocytes, and inserting them into normal lymphocytes that we have in enormous numbers (1 million in every drop of blood) – explains Rosenberg – we can generate all the anti-cancer cells we want.”
In a larger phase 2 trial, 7 patients with metastatic colon cancer were treated with this experimental personalized cellular immunotherapy. Before treatment, all 7 received different doses of the immunotherapy drug pembrolizumab, and after treatment they were given another immunotherapy (IL-2). The result: 3 patients had a substantial reduction in metastatic tumors in the liver, lungs and lymph nodes, which lasted 4 to 7 months. The median time to disease progression was 4.6 months. Of the 3 patients who responded to the treatment, Rosenberg notes, 2 had received receptors derived from cytotoxic T lymphocytes, the main ‘killers’ of diseased cells. Therefore, researchers are looking for ways to insert T-cell receptors into specific subtypes of normal lymphocytes, to improve their reactivity.
Colon cancer is just one of many solid tumors that scientists are studying. The project is ongoing and includes patients with several types of solid tumors, the NIH says. “This is just the beginning of the process of converting normal lymphocytes into cells that can treat common solid tumors,” Rosenberg says. “This study shows that it is possible, and once you know that,” he says, “you can work to do it better.”
