Adoptive T-Cell Therapy Next Step in Treating Melanoma

Induced pluripotent stem cells (iPSC) may provide an unlimited number of phenotypically defined, functional and expandable autologous antigen-specific T cells with the characteristics needed to combat cancer, according to a new study published in Cancer Research.  

Adoptive T-cell therapy has emerged as a possible treatment for patients with metastatic melanoma. However, efforts to apply these advances clinically have been limited by difficulties in obtaining long-lasting T cells that can survive following infusion.

A team of researchers from Roswell Park Cancer Institute (RPCI), the University of Michigan, and Kyoto University have found promising results with the first successful generation of iPS cells from melanoma-targeting T cells in a preclinical study. They report on the first successful programming of T-cell receptor (TCR) transgenic CD8+ T-cells into pluripotency.

“Our findings are highly encouraging, and we expect that this work will provide the foundation for developing personalized, immune-based therapies for patients with advanced and metastatic melanoma,” said study investigator Fumito Ito, MD, PhD, Assistant Professor of Oncology in the Department of Surgical Oncology, in a RPCI news release. “We plan to further develop this strategy using T cells derived from engineered iPS cells, and looking not only at melanoma but at other types of cancer.”

The researchers write that iPSC can be reprogrammed to function like embryonic stem cells and they hold great promise in the field of regenerative medicine. Most notably, iPSC are long-lasting and can be made to differentiate into a wide range of tissues. It is hoped they can be stored for use in generating an unlimited number of patient-specific T cells for use in cancer immunotherapy. 

Dr. Ito and his team established a syngeneic mouse model for evaluating in vitro and in vivo antitumor reactivity of regenerated T cells from iPSC bearing a rearranged TCR of known antigen specificity. The researchers found that TCR retained T-cell derived iPSC and they differentiated into CD4+CD8+ T cells.  Further, these cells expressed CD3 and the desired TCR in vitro. The authors report that these adoptively transferred iPS cell-derived T cells evaded immune rejection as well as mediated regression of large tumors. They also improved survival of the lab models studied and established antigen-specific immunological memory.

The researchers are hoping this therapeutic approach will be effective long-term, which so far has been achievable.