Cellular Immunotherapy Offers Hope for Solid Tumors

Early results from a small clinical trial suggest that metastatic solid tumors may respond well to a novel cellular immunotherapy strategy. The National Institutes of Health (NIH) genetically modified each patient’s normal white blood cells, or lymphocytes, to develop receptors that identify and target the patient’s particular cancer cells. These preliminary results are from patients who had previously received several prior therapies for metastatic colorectal cancer. In multiple individuals, the customized immunotherapy reduced the size of their tumors and prevented them from growing again for a maximum of seven months. The results were released in Nature Medicine on July 11, 2024.

Tumor-infiltrating lymphocyte (TIL) therapy has been demonstrated to be effective against metastatic melanoma, whereas chimeric antigen receptor (CAR) T-cell therapy has already demonstrated efficacy against some blood malignancies. However, according to Steven A. Rosenberg, M.D., Ph.D. of NCI’s Center for malignancy Research (CCR), who co-led the study with Maria Parkhurst, Ph.D. of CCR’s Surgery Branch, a successful cellular therapy against any other solid malignancy has proven elusive thus far.

“The fact that we can take a growing metastatic solid cancer and get it to regress shows that the new cellular immunotherapy approach has promise. However, it’s important to understand that these findings are preliminary and that the approach needs to be further refined and tested in more types of solid cancers.”- Steven A. Rosenberg, Center for Cancer Research, NCI

The novel method solves two problems with cellular immunotherapy: how to generate a large quantity of T cells with particular cancer cell recognition and how to increase the capacity of these altered T cells to proliferate after being given back to the patient.

Dr. Rosenberg and his colleagues collected lymphocytes from each patient’s tumor for the investigation. They next identified and isolated T-cell receptors—receptors on those lymphocytes that recognized particular alterations in each patient’s tumor—using advanced molecular characterisation techniques. Following the genetic sequencing of those receptors, normal cells obtained from each patient’s circulating blood were infected with the receptor’s genes using a retrovirus.

After being cultivated to hundreds of millions in the lab, the genetically altered lymphocytes were reinfused into the patients, where they continued to proliferate and express the tumor-specific T-cell receptors.

“By taking the natural T-cell receptors that are present in a very small number of cells and putting them into normal lymphocytes for which we have enormous numbers-;a million in every thimbleful of blood-;we can generate as many cancer-fighting cells as we want,” Dr. Rosenberg explained.

Personalized cellular immunotherapy was used to treat seven patients with metastatic colon cancer as part of a larger phase 2 investigation. The seven were administered multiple doses of pembrolizumab, an immunotherapy drug, before to cell therapy, and IL-2, another immunotherapy drug, following the therapy. For four to seven months, three patients experienced a significant reduction in the size of their metastatic tumors in their lymph nodes, liver, and lungs. The condition progressed over a median of 4.6 months.

Two of the three patients that responded to treatment, according to Dr. Rosenberg, had received T-cell receptors generated from cytotoxic T cells, which are mostly in charge of eliminating sick cells. According to Dr. Rosenberg, his research group is investigating ways to enhance the reactivity of normal lymphocyte subtypes by introducing T cell receptors.

Among the numerous solid tumors under investigation by the researchers is colon cancer. Patients with several solid cancer types are part of the current trial.

“It’s just the very beginning of converting normal lymphocytes into cells capable of treating the common solid cancers,” said Dr. Rosenberg. This investigation demonstrates that it is feasible. You try to make it better as soon as you realize it’s feasible.”

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