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Blood, 1 July 2003, Vol. 102, No. 1, pp. 4
  T cells in cancer immunotherapy
The largest subset of human   T cells is the V2 (alternate V9) V2 subset, comprising 2% to 5% of peripheral blood T cells. These V2V2 T cells uniformly recognize nonpeptide alkylamine, nitrogen-containing bisphosphonate, and organophosphate antigens in a T cell receptor (TCR)—dependent fashion. Such recognition enhances T cell—mediated cytotoxicity, and secretion of IFN- and TNF- , which are important antitumor effector mechanisms (Morita et al, Springer Sem Immunopath. 2000;22:191-217).
Mouse models provide strong evidence for T cell—mediated resistance to tumors and infection. In humans, certain lymphoma and myeloma cells display cell-surface antigens that are recognized in a V2V2 TCR-dependent manner. Others display nonclassical major histocompatibility complex (MHC) class I—related proteins such as MHC class I—related chain A (MICA) and UL16 binding proteins (ULBPs) that can be recognized by NKG2D receptors on activated T cells. Cells from common cancers metastatic to bone, such as those from breast cancer and prostate cancer, can be exposed to large concentrations of bone-avid nitrogen-containing bisphosphonates, such as pamidronate and risedronate. Such exposure may kill these cells directly, in several days, but T cells can kill these sensitized cells in a matter of minutes. Thus, bisphosphonates can at once activate T cells and sensitize tumor cells for elimination by T cells (Das et al, Blood. 2001;98:1616-1618). Treatment of multiple myeloma with pamidronate has increased survival and decreased the incidence of metastatic lesions and pathologic fractures (Berenson et al, J Clin Oncol. 1998;16:593-602).
In this issue, Wilhelm and colleagues (page 200) report successful treatment of refractory lymphoma and myeloma with pamidronate and interleukin 2 (IL-2). Importantly, objective clinical responses correlated with proliferation of T cells in vivo, strongly suggesting a role for T cells in mediating the response. As more potent T-cell antigens are coupled with treatments earlier in disease, we can soon expect even better results. These data represent an important initial step in manipulating T cells in vivo to treat tumors and, perhaps, to treat or prevent infections that accompany them.
Jack F. Bukowski
Brigham and Women's Hospital
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T cells for immune therapy of patients with lymphoid malignancies
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Blood 2003 102: 200-206.
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