Second-generation anti-carcinoembryonic antigen designer T cells resist activation-induced cell death, proliferate on tumor contact, secrete cytokines, and exhibit superior antitumor activity in vivo: a preclinical evaluation.

Purpose: This report describes the development and preclinical qualification tests of second-generation anti-carcinoembryonic (CEA) designer T cells for use in human trials.

Experimental Design: The progenitor first-generation immunoglobulin-T-cell receptor (IgTCR) that transmits Signal 1-only effectively mediated chimeric immune receptor (CIR)-directed cytotoxicity, but expressor T cells succumbed to activation-induced cell death (AICD). The second-generation CIR (termed "Tandem" for two signals) was designed to transmit TCR Signal 1 and CD28 Signal 2 to render T cells resistant to AICD and provide prolonged antitumor effect in vivo.

Induction of CD4-independent E7-specific CD8+ memory response by heat shock fusion protein.

Infection with human papillomavirus type 16 (HPV16) is strongly associated with a number of disease states, of which cervical and anal cancers represent the most drastic endpoints. Induction of T-cell-mediated immunity, particularly cytotoxic T lymphocytes (CTL), is important in eradication of HPV-induced lesions. Studies have shown that heat shock protein fusion proteins are capable of inducing potent antigen-specific CTL activity in experimental animal models.

PAQR proteins: a novel membrane receptor family defined by an ancient 7-transmembrane pass motif.

An emerging series of papers has identified new receptor proteins that predict seven-transmembrane pass topologies. We have consolidated this family to 11 human genes and have named the family PAQR, after two of the initially described ligands (progestin and adipoQ receptors). This protein family has ancient evolutionary roots, with identified homologs found in eubacteria.

The complete complement of C1q-domain-containing proteins in Homo sapiens.

The C-terminal domains of the A, B, C chains of C1q subcomponent of C1 complex represent a common structural motif, the C1q domain, that is found in a diverse range of proteins. We analyzed the human genome for the complete complement of this family and have identified a total of 31 independent gene sequences. The predominant organization of C1q-domain-containing (C1qDC) proteins includes a leading signal peptide, a collagen-like region of variable length, and a C-terminal C1q domain.

Generating potent Th1/Tc1 T cell adoptive immunotherapy doses using human IL-12: Harnessing the immunomodulatory potential of IL-12 without the in vivo-associated toxicity.

Interleukin (IL)-12 is a cytokine originally identified from medium conditioned by an Epstein-Barr virus transformed cell line. IL-12 has been shown to increase IFN-gamma secretion from NK and T cells, significantly enhance cytolytic activity in both of these cell types, and promote the development of Th1/Tc1 immune responses. These properties make IL-12 an attractive candidate for the development of various clinical protocols ranging from the treatment of viral diseases to tumor immunotherapy.

Adenoviral-mediated gene transfer of lymphotactin to the lungs of mice and rats results in infiltration and direct accumulation of CD4+, CD8+, and NK cells.

Chemokines are small 8-12-kDa chemotactic cytokines that were initially characterized for their ability to control leukocyte trafficking and, to a lesser extent, leukocyte function. Lymphotactin was first described as a T lymphocyte-specific chemotactic factor. However, it has since been shown to also be a potent attractant for natural killer (NK) cells.