New Approach Discovered to Fight One of the Deadliest Forms of Lung Cancer

A team from the Walter and Eliza Hall Institute of Medical Research (WEHI) found that specialized immune cells known as gamma delta T cells can attack tumors that escape recognition by conventional immune cells. The researchers also discovered that some existing drugs may enhance the cancer-fighting activity of these lymphocytes.

Small cell lung cancer is considered one of the most aggressive forms of cancer. Despite advances in immunotherapy for other types of cancer, only a small proportion of patients with this tumor achieve long-term benefits from such treatment. One reason is that cancer cells can become virtually invisible to the immune mechanisms targeted by existing therapies.

"For decades, we have known that small cell lung cancer is exceptionally good at hiding from the immune system. We have identified immune cells that appear capable of recognizing this disguise," said the study's senior author, Professor Kate Sutherland of WEHI.

The researchers created miniature tumor models in the laboratory using tissue samples donated by patients through the Victorian Cancer Biobank, in collaboration with the Royal Melbourne Hospital. When gamma delta T cells obtained from the same patients' blood were added to these models, the immune cells effectively recognized and destroyed the tumor cells.

The team then tested two drugs: tarlatamab, which is already approved for the treatment of small cell lung cancer, and zoledronate, which is used to treat osteoporosis and certain cancer-related bone conditions.

Zoledronate increased the number of gamma delta T cells and enhanced their ability to recognize tumors. Tarlatamab, in turn, helped the immune cells interact more closely with cancer cells. Combined, the drugs significantly strengthened the attack on tumor cells in laboratory models.

According to the study's first author, Jin Ng, the findings also suggest that these lymphocytes could be used in cell therapy. This approach would involve growing large numbers of the cells outside the body and then administering them to patients. It could potentially benefit people who have low numbers of gamma delta T cells to begin with.

The researchers developed this hypothesis after analyzing data from two major clinical trials, IMpower133 and CASPIAN, which helped establish immunotherapy as part of standard treatment for small cell lung cancer. Patients who benefited most from immunotherapy showed stronger signs of gamma delta T cell presence.

The scientists plan to continue their research to determine whether these mechanisms can be harnessed to develop new immunotherapy treatments. However, the findings do not mean that the new drug combination has been proven effective in patients. Its potential will need to be evaluated in further clinical trials.