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J. Exp. Med.,
Volume 188, Number 4, August 17, 1998 619-626
By
From the * Department of Human Genetics, Most tumor cells function poorly as antigen-presenting cells in part because they do not express
costimulatory molecules. To provide costimulation to T lymphocytes that recognize tumor cells, we constructed a CD28-like receptor specific for GD2, a ganglioside overexpressed on the
surface of neuroblastoma, small-cell lung carcinoma, melanoma, and other human tumors.
Recognition of GD2 was provided by a single-chain antibody derived from the GD2-specific
monoclonal antibody 3G6. We demonstrate that the chimeric receptor 3G6-CD28 provides
CD28 signaling upon specific recognition of the GD2 antigen on tumor cells. Human primary
T lymphocytes retrovirally transduced with 3G6-CD28 secrete interleukin 2, survive proapoptotic culture conditions, and selectively undergo clonal expansion in the presence of an antiidiotypic antibody specific for 3G6-CD28. Polyclonal CD8+ lymphocytes expressing 3G6-CD28
are selectively expanded when cultured with cells expressing allogeneic major histocompatibility complex class I together with GD2. Primary T cells given such an antigen-dependent survival advantage should be very useful to augment immune responses against tumor cells.
Department of Pediatrics, and § Immunology Program,
Memorial Sloan-Kettering Cancer Center, New York 10021
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