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Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation
Published on: January 14, 2011
Augmented lymphocyte expansion from solid tumors with engineered cells for costimulatory enhancement
Kevin M Friedman1, Laura E Devillier, Steven A Feldman
1Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda 20892-1201, MD, USA.
Journal of Immunotherapy (Hagerstown, Md. : 1997)
|October 13, 2011
Summary
Engineered cells for costimulatory enhancement (ECCE) significantly improve tumor-infiltrating lymphocyte (TIL) expansion from melanoma biopsies. This advance enhances TIL therapy accessibility for more patients by increasing reliable TIL generation.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Adoptive T-cell therapy, including tumor-infiltrating lymphocyte (TIL) therapy, is crucial for treating melanoma.
- Current methods for TIL expansion from tumor biopsies face challenges in efficiency and reliability, limiting patient access.
- Artificial antigen-presenting cells have been explored for their costimulatory properties in T-cell expansion.
Purpose of the Study:
- To investigate the efficacy of engineered cells for costimulatory enhancement (ECCE) in improving TIL expansion from melanoma biopsies.
- To determine if ECCE can enhance the number and phenotype of TILs compared to standard interleukin-2 expansion.
- To assess the potential of ECCE for broader application in TIL therapy beyond melanoma.
Main Methods:
- Development of ECCE using K562 cells engineered to express 4-1BBL without artificial antigen presentation.
- Processing of single-cell suspensions from melanoma biopsies to generate TIL cultures.
- Comparison of TIL expansion, cell counts, and phenotype (CD8CD62L, CD8CD27) between ECCE-supplemented and standard interleukin-2-expanded cultures.
- Evaluation of ECCE's effectiveness on non-melanoma tumor cell suspensions.
Main Results:
- ECCE significantly accelerated TIL expansion and increased TIL numbers from single-cell melanoma suspensions (P=0.001).
- TILs generated with ECCE exhibited higher proportions of CD8CD62L and CD8CD27 T cells compared to those expanded with interleukin-2 alone.
- ECCE-enhanced TILs maintained their antitumor reactivity.
- Similar improvements in TIL expansion were observed using ECCE with non-melanoma tumor cell suspensions.
Conclusions:
- ECCE is a potent strategy for enhancing TIL expansion and improving TIL generation reliability.
- The use of ECCE can broaden patient eligibility for TIL therapy by overcoming current production limitations.
- ECCE represents a promising advancement for adoptive T-cell therapy, potentially applicable to various cancer types.
