Masters of Immunology
Yifeng Xia, Shen Shen and Inder M. Verma
Cancer Immunol Res September 1 2014 2 (9) 823-830; DOI:10.1158/2326-6066.CIR-14-0112
Litterman and colleagues created a cocktail of cytokines and small molecules for ex vivo expansion of naïve or antigen-specific T cells into polyclonal cytotoxic T cells with memory phenotype, and greater proliferative and antitumor activity in vivo.
Wang and colleagues describe the development and comprehensive preclinical characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor blocking mAb, the antitumor activity and safety profile of which has been demonstrated in human clinical trials in various solid tumors.
Tepsuporn, Hu, and colleagues generated the first mouse models for B-cell lymphoma in the context of ATM deficiency, and they provide a detailed characterization of the mature B-cell lymphomas that arise, revealing an unanticipated mechanism for the developmental propagation of V(D)J recombination-initiated DNA double-strand breaks.
Schrand and colleagues report the efficacy in five murine tumor models of an immunotherapeutic approach whereby systemic administration of tumor stroma-targeted 4-1BB aptamer conjugates, which target disseminated tumor lesions, elicits potent antitumor immunity with minimal dose-limiting toxicity.
Du and colleagues report that a “missing ligand” genotype predictive of unlicensed NK cells was associated with higher progression-free survival in 101 follicular lymphoma patients treated with rituximab-containing mAb combinations, and that rituximab triggered responses in vitro from healthy-donor unlicensed NK cells.
Ohmatsu and colleagues report the consistently high and increasing expression of IL32 in cutaneous T-cell lymphoma mycosis fungoides (MF) compared with benign inflammatory skin diseases, and these findings correlate with increases in IFNγ mRNA, suggesting that IL32 may be an autocrine cytokine in MF progression.
Chandra, Quispe-Tintaya, and colleagues show that stimulator of IFN genes (STING) ligand c-di-GMP activated caspase-3, stimulated T cells, and nearly completely eliminated all metastases in mouse breast cancer model 4T1, when combined with Listeria monocytogenes–based Mage-b vaccine in a therapeutic setting.
Chen and colleagues developed an improved, attenuated L. monocytogenes–based vaccine that induced the regression of established mouse TC-1 tumors; they show that listeriolysin O serves as a vaccine adjuvant that decreases Treg frequency by inducing the expansion of non-Treg T cells.