In vitro studies may be useful in donor selection and evaluating the effectiveness of CD8+ T-cell reprogramming: experience of a pilot study

Circulating tumor cells (CTCs) are detected before the appearance of other signs of lung cancer, including precancerous conditions. CTCs and cancer stem cells (CSCs) play a leading role in metastasis of small cell lung cancer (SCLC) and can be used as diagnostic and prognostic markers, potential therapeutic targets. Cell therapy with modified immune cells is a promising approach for the treatment of SCLC. An unresolved issue of this approach to therapy is the choice of the optimal cell donor whose modified cells could eliminate the given target of CSCs. In the present study, using in vitro allogeneic and autologous cell therapy model, we reprogrammed CD8⁺ T-cells isolated from the blood of healthy volunteers (non-smoker and smoker) and patients with chronic lung diseases (chronic obstructive pulmonary diseases (COPD), SCLC and asthma in different combination) and assessed their survival and cytotoxic activity relative to CSCs of a patient with SCLC and COPD. Reprogramming with MEK and PD-1 inhibitors, and targeted “training” with CSCs isolated from the blood of the patient with SCLC and COPD increased the survival and cytotoxic activity of allogeneic CD8⁺ T-cells from all subjects in vitro. At the same time, the positive effect of reprogramming is more pronounced in patients with lung diseases that in healthy donors. Autologous reprogrammed CD8⁺ T-cells was shown to be highly effective in eliminating CSCs in a patient with SCLC and COPD. Thus, in vitro studies are significant in selection of a potential cell donor and evaluating the effectiveness of their reprogramming.