# Natural and revolutionary tumor-specific T-cell therapy

## TL;DR

A new T-cell therapy was developed that avoids viruses and professional antigen-presenting cells, showing promise in targeting tumors without causing secondary cancers.

## Contribution

A novel tumor-specific T-cell therapy was developed without using lentivirus or professional APCs, enabling safer and more specific cancer treatment.

## Key findings

- Tumor-specific T-cells were generated by co-culturing MHC+ cancer cells and naïve T-cells with CD28 signals.
- The therapy reduced tumor nodules by 90% and improved survival in mice.
- Tumor-specific T-cells could be easily separated and produced from peripheral blood.

## Abstract

Recently the FDA conducted a risk investigation and labeled the Boxed Warning for all BCMA- and CD19-directed CAR-T cell therapy, so does it mean that the public must take risk of secondary cancer to receive cell therapy? Here, without lentivirus and professional antigen presenting cell application, a novel tumor-specific T-cell therapy was successfully developed only by co-culturing MHC+ cancer cells and Naïve-T cells under the CD28 co-stimulatory signals. These tumor-specific T-cells could be separated through cell size and abundantly produced from peripheral blood, and would spontaneously attack target cells that carrying the same tumor antigen while avoiding others in vitro test. Moreover, it markedly decreased 90% tumor nodules companying with greatly improving overall survival (76 days vs 30 days) after twice infusion back to mice. This work maximally avoided the risks of secondary cancer and non-specific killing, and might open a revolutionary beginning of natural tumor-specific T-cell therapy.

The online version contains supplementary material available at 10.1007/s13659-024-00472-w.

Tumor specific T-cell generation without lentivirus and professional APC application.Only by co-culturing MHC+ cancer cell and Naïve-T cell supplying CD28 signal.Easy separation by cell size and fast generation from peripheral blood.Maximally avoid troubles of viral safety and non-specific reaction.Novel model of T-cell activation could be used to bioprospect medicinal molecules instead of CD28 from abundant natural products.

Tumor specific T-cell generation without lentivirus and professional APC application.

Only by co-culturing MHC+ cancer cell and Naïve-T cell supplying CD28 signal.

Easy separation by cell size and fast generation from peripheral blood.

Maximally avoid troubles of viral safety and non-specific reaction.

Novel model of T-cell activation could be used to bioprospect medicinal molecules instead of CD28 from abundant natural products.

The online version contains supplementary material available at 10.1007/s13659-024-00472-w.