There is evidence showing that high avidity CTLs can be more effective than low avidity CTLs for adoptive tumor immunotherapy. Because many T cell-recognized tumor antigens are nonmutated self-proteins, tolerance mechanisms are likely to render high avidity T cells unresponsive or cause T cell elimination by clonal deletion. We recently used the allo-restricted strategy to circumvent immunologi...

PURPOSE The antitumor activity of chimeric antigen receptor (CAR)-redirected CTLs should be enhanced if it were possible to increase their proliferation and function after adoptive transfer without concomitantly increasing the proliferation and function of regulatory T cells (Treg). Here, we explored whether the lack of IL-7Rα in Treg can be exploited by the targeted manipulation of the interle...

Transforming growth factor (TGF), a pleiotropic cytokine that regulates cell growth and differentiation, is secreted by many human tumors and markedly inhibits tumor-specific cellular immunity. Tumors can avoid the differentiating and apoptotic effects of TGFby expressing a nonfunctional TGFreceptor. We have determined whether this immune evasion strategy can be manipulated to shield tumor-spec...

Although CTLs bear main immune responses in human tumors, stable CTL clones against human lung cancer have rarely been generated. Our previous study demonstrated efficient autologous CTL induction in human gastric cancer and glioblastoma by cytokine combination of interleukin (IL)-1beta (167 IU/ml), IL-2 (67 IU/ml), IL-4 (67 IU/ml), and IL-6 (134 IU/ml). In this study, we demonstrated successfu...

PURPOSE The interleukin-13 receptor alpha 2 (IL-13R alpha 2) is a glioma-restricted cell-surface epitope not otherwise detected within the central nervous system. Here, we report a novel approach for targeting malignant glioma with IL-13R alpha 2-specific CTLs. EXPERIMENTAL DESIGN Artificial antigen-presenting cells (aAPC) were made by coating human leukocyte antigen (HLA)-A2/pIL-13R alpha 2(...

We investigated whether Toll-like receptor ligands (TLR-Ls) can bypass the requirement for CD4(+) T-cell help in the induction of fully efficient memory CD8(+) T cells (cytotoxic T lymphocytes [CTLs]). "Helpless" CTLs were induced by a synthetic CD8(+) T-cell epitope administered with TLR3-L and TLR9-L, but not with TLR2/6-L, TLR4-L, or TLR7-L. The up-regulation of MHC-I and costimulatory molec...

Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown that MID1 is strongly up-regulated in murine cytotoxic T lymphocytes (CTLs), and that it has a significant i...

How cytotoxic T lymphocytes (CTLs) kill intracellular pathogens without killing themselves has been a recurring question ever since their discovery. By using mice deficient in Serine Protease Inhibitor 6 (Spi6), we show that by inhibiting granzyme B (GrB), Spi6 protects CTLs from self-inflicted injury. Infection with either Lymphocytic Choriomeningitis virus (LCMV) or Listeria monocytogenes (LM...

Understanding interfacial charge transfer processes such as trap-mediated recombination and injection into transport layers (CTLs) is crucial for the improvement of perovskite solar cells. Herein, we reveal that chemical binding to CH3NH3PbI3 defect sites an integral part mechanism in both n-i-p p-i-n architectures. Specifically, use a mixture optical X-ray photoelectron spectroscopy show inter...

BACKGROUND A limitation with current imaging strategies of recurrent glioma undergoing radiotherapy is that tumor and radiation injury cannot be differentiated with post contrast CT or MRI, or with PET or other more complex parametric analyses of MRI data. We propose to address the imaging limitation building on emerging evidence indicating that effective therapy for recurrent glioma can be att...