Adoptive T-cell therapy (ACT) utilizes tumor-reactive T cells to induce disease remission. While ACT has been used effectively to treat metastatic melanoma and certain epithelial cancers, most patients do not respond to treatment. Although the mechanisms underlying this variable response to therapy are not fully elucidated, the phenotype of the adoptively transferred cell is known to be a key determinant of treatment efficacy.
Researchers at National Cancer Institute’s (NCI) Surgery Branch have now determined that the CD3+CD39-CD69- subpopulation of T cells are highly associated with complete disease response following ACT. Leveraging over 30 years of ACT clinical data and associated biological materials, NCI researchers immune-profiled archived infusion products and correlated cell phenotypes with therapeutic outcomes. Clustering of clinically significant markers helped in determining the candidate profile. Validation of the markers in other patients and other cancer settings is ongoing.
The inventive method could be used to engineer relevant cell therapy products in multiple disease settings, including, but not limited to, cancer and acute and chronic infectious diseases. The method could further be used to develop gene expression signatures to either screen prospective patients or genetically engineer better therapies. In addition to its application in ACT, the “response” immunoprofile may be applicable to immunotherapy regimens more generally, including checkpoint blockade therapies, immune modulators, and T-cell receptor (TCR) or chimeric antigen receptor (CAR) therapies.
The NCI seeks applications from parties interested in co-developing and/or licensing this method to develop improved cancer immunotherapies. Related technologies are available.
- Companion diagnostic to support cell therapy and utility products in multiple disease settings, including, but not limited to, cancer and acute and chronic infectious diseases
- Generation of gene expression signatures to prospectively screen patients or to engineer better ACT and TCR-based treatments
- Immunoprofiling patients before and after ACT, checkpoint blockade, immunomodulator, and TCR/CAR therapies
- Method to screen adoptive T-cell therapy (ACT) patients to predetermine therapy efficiency
- Method to increase the efficacy of ACT therapies
Frank Joseph Lowery Ph.D. (NCI), Steven Aaron Rosenberg MD, PHD (NCI), Gregoire Yves Altan-Bonnet Ph.D (NCI), Sri Krishna Ph.D (NCI), Paul F Robbins PH.D (NCI)
Krishna S, et al. Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer. [PMID 33303615]
- U.S. Provisional: U.S. Provisional Patent Application Number 63/075,536 , Filed 08 Sep 2020