ALL STEM CELLS

Personalized Immunotherapy

written by Steven A. Rosenberg
National Cancer Institute, NIH


Adoptive cell transfer (ACT) uses patient’s lymphocytes to treat their autologous cancer. When tumor infiltrating lymphocytes are used for ACT, they can mediate complete, likely curative, regression in patients with metastatic melanoma.
Lymphocytes genetically engineered to express anti-tumor receptors can treat patients with refractory lymphomas and leukemias. However, the majority of metastatic epithelial cancers are still resistant to immunotherapy. Recent approaches using deep exome sequencing along with high-throughput immunologic testing opened the door to treat these common types of cancer and to identify the rare somatic mutations that are immunogenic.
ACT targeting these mutations is the ultimate ‘‘personalized’’ cancer treatment but is contrary to the mantra of many pharmaceutical companies who want ‘‘drugs in a vial’’ that can be mass produced and distributed. Although this approach has produced drugs that prolong the life of patients with solid metastatic cancers, curative treatments are rare and have had limited impact on overall death rates from cancer. A highly ‘‘personalized’’ immunotherapy for common cancers may require the development of a unique drug (autologous lymphocytes) for each patient. It will also need major changes and considerable flexibility on the part of industry. The effectiveness of treatment should trump simplicity of production and convenience of administration if progress is to be made in enabling patients with metastatic cancer to be cured and relish a normal lifespan.