Intrathymic Selection: New Insight into Tumor Immunology

Kazansky, Dmitry

doi:10.1007/978-0-387-72005-0_14

Cited by 8 publications

(9 citation statements)

References 50 publications

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“…However, when these peptide is from non-mutated differentiation antigens, it is not sufficient to simulate persistent and robust anti-tumor CTL responses [28, 29]. This is due to immune tolerance mechanisms which generally inhibit or remove high activity auto-reactive T cells [30]. Therefore, bulk tumor-specific CTL, especially those which recognize non-mutated tumor-specific antigens, are removed at the thymus and at the periphery.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic carcinoma-specific immunotherapy using novel tumor specific cytotoxic T cells

Liu

Jiang

et al. 2016

Oncotarget

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Pancreatic cancer represents one of the most lethal human cancers. Investigation of the effective targeting to the tumor cells is essential for both primary tumors and metastases. Tumor specific cytotoxic T lymphocytes (CTLs) have recently been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern of CTL carrying the lentiviral vectors with the characteristic of adenoviral E1 gene under the control of the cell activation-dependent CD40 ligand promoter (Lenti/hCD40L/E1AB). Following transduction with adenoviral particles containing chimeric type 5 and type 35 fiber proteins (Ad5/35-TRAIL), these CTLs produced infectious virus when exposed to SW1990 cells. We found that the novel CTL harboring Lenti/hCD40L/E1AB and Ad5/35-TRAIL inhibited pancreatic cancer cell growth and angiogenesis in vitro and in vivo. Furthermore, Ad5/35-TRAIL transduced CTL induced significant apoptosis in pancreatic carcinoma cell lines and upregulated IFN-gamma (IFN-γ) secretion of CTLs. Importantly, Ad5/35-TRAIL transduced CTLs had no inhibitory effect on normal cells. Thus, the novel CTLs may be safe and feasible for the development of gene therapy approaches to pancreatic carcinoma.

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Section: Discussionmentioning

confidence: 99%

Pancreatic carcinoma-specific immunotherapy using novel tumor specific cytotoxic T cells

Liu

Jiang

et al. 2016

Oncotarget

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“…Бόль-шие возможности для диагностики и иммунотерапии онкологических заболеваний представляет группа опу-холеассоциированных антигенов -нормальных не-мутантных белков, которые экспрессируются в транс-формированных клетках, но редко встречаются или слабо экспрессируются в нормальных клетках орга-низма. Главная проблема в стимуляции иммунного ответа на такие антигены состоит именно в том, что они представляют собой нормальные белки организ-ма, толерантность к которым развивается в процессе внутритимусной селекции, отбирающей клоны с низко-аффинными рецепторами к «своему» [73,74]. Вместе с тем в медуллярном эпителии тимуса имеет место экс-прессия широкого спектра сугубо тканеспецифичес-ких белков, включая антигены группы testis, контро-лируемые геном Aire [75][76][77].…”

Section: обзорные статьиunclassified

Transplantational and specific antitumor immunity in retrospective view: new models based on transgenesis of individual chains of T-cell receptor

Kazanskii¹,

Силаева²,

Kalinina³

et al. 2016

Usp. mol. onkol

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“…melanosomal proteins) , it can be insufficient to engender robust and sustained anti-tumor CTL responses (6, 7). This is a result of immune tolerance mechanisms that generally suppress or eliminate high avidity auto-reactive T cells (8). As a result of these mechanisms, the vast majority of tumor-specific CTL, specifically those that recognize non-mutated tumor-associated antigens, are eliminated in the thymus and in the periphery.…”

Section: Introductionmentioning

confidence: 99%

Conditional Superagonist CTL Ligands for the Promotion of Tumor-Specific CTL Responses

Abdul-Alim

Yee

2010

The Journal of Immunology

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While it has been demonstrated that cytotoxic T lymphocytes (CTL) can be raised against tumor-associated self-antigens, achieving consistent and effective clinical responses has proven challenging. Superagonist altered peptide ligands (APL) can often elicit potent anti-tumor CTL responses where the native tumor-associated epitope fails. Current methods have identified a limited number of superagonist APLs, including the prototypic 27L mutant of MART-1. However, more comprehensive screening strategies would be desirable. In this study we utilize a novel genetic screen, involving recombinant technology and class I antigen cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant by surveying the effectiveness of virtually every single amino acid substitution mutant of 27L to activate human antigen-specific CTL clones recognizing the wild-type MART-126-35 epitope. We identify 3 novel mutant epitopes with superagonist properties that are functionally superior to 27L; however, the ability of a given analog to act as superagonist varies among patients and suggest that a given superagonist altered peptide ligand may be ideally suited to different patients. These findings endorse the use of comprehensive methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients.

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Intrathymic Selection: New Insight into Tumor Immunology

Cited by 8 publications

References 50 publications

Pancreatic carcinoma-specific immunotherapy using novel tumor specific cytotoxic T cells

Pancreatic carcinoma-specific immunotherapy using novel tumor specific cytotoxic T cells

Transplantational and specific antitumor immunity in retrospective view: new models based on transgenesis of individual chains of T-cell receptor

Conditional Superagonist CTL Ligands for the Promotion of Tumor-Specific CTL Responses

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