Download Developments in T Cell Based Cancer Immunotherapies by Paolo A. Ascierto, David F. Stroncek, Ena Wang PDF

By Paolo A. Ascierto, David F. Stroncek, Ena Wang

This quantity illustrates the salient facets of melanoma biology proper to the profitable implementation of immunotherapy. subject matters contain enhancement of antigen-specific immune responses via anti-cancer vaccines, modulation of the functionality of T cells in the tumor microenvironment, and the consequences of genetic, epigenetic, developmental, and environmental determinants on T mobilephone functionality. different themes lined comprise the ex vivo enlargement of T or different immune cells and their genetic amendment or reprogramming to extend their skill to outlive and extend while adoptively transferred again to the sufferers. particular consciousness is dedicated to the genetic manipulation of T cells in the course of the advent of re-directed T telephone receptors, chimeric antibody receptors, and different genetic manipulation geared toward enhancing their effectiveness as anti-cancer brokers. moreover, the progressive position of checkpoint inhibitors and their strength together with different immunotherapeutic methods or with general chemo and radiation remedy are broadly mentioned.

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Chianese-Bullock KA, Pressley J, Garbee C et al (2005) MAGE-A1-, MAGE-A10-, and gp100-derived peptides are immunogenic when combined with granulocyte-macrophage colony-stimulating factor and Montanide ISA-51 adjuvant and administered as part of a multipeptide vaccine for melanoma. J Immunol 174:3080–3086 4. Slingluff CL Jr, Petroni GR, Olson WC et al (2009) Effect of granulocyte/macrophage colony-stimulating factor on circulating CD8+ and CD4+ T-cell responses to a multipeptide melanoma vaccine: outcome of a multicenter randomized trial.

PD-1 is expressed on activated T cells, B cells, and some myeloid cells. Its ligand, PD-L1, is expressed on some peripheral tissues and many types of tumors. PD-L2 is expressed on DCs. PD-L1 expression on peripheral tissues appears essential to maintaining peripheral tolerance. The interaction of PD-1 with PD-L1/PD-L2 can suppress T-cell activation, while blocking this interaction can restore immune function [167, 168]. In a phase I clinical trial, 296 patients with a variety of cancers (advanced melanoma, NSCLC, castration-resistant prostate cancer, RCC, and colorectal cancer) were treated with anti-PD-1 antibody (BMS-936558 or MDX-1106) [169].

Thus, unlike most existing vaccines, one cannot simply mimic the disease agent to make a successful vaccine, but instead may need to combine several approaches. Our lab has developed a pushpull strategy in which we first improve the immunogenicity of the antigens themselves by modifying the amino acid sequence to improve binding of epitopes to MHC molecules (a process called epitope enhancement). The next step is to “push” the response to improve not only the quantity but also the quality of the immune response, to achieve better avidity, longevity, and type of response, by using combinations of defined molecular adjuvants such as cytokines like IL-15, TLR ligands, and NKT cell agonist antigens.

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