scholarly journals Tumour, Oxidative Stress and Host T Cell Response: Cementing the Dominance

2015 ◽  
Vol 82 (6) ◽  
pp. 477-488 ◽  
Author(s):  
S. Bhattacharyya ◽  
J. Saha
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response

scholarly journals Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells

2021 ◽  
Vol 9 (6) ◽  
pp. 1219
Author(s):  
Maria Isaguliants ◽  
Olga Krotova ◽  
Stefan Petkov ◽  
Juris Jansons ◽  
Ekaterina Bayurova ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Cell Response ◽  
Mammalian Cells ◽  
Metastatic Potential ◽  
T Cell Response ◽  
Dna Immunization ◽  
Drug Resistant ◽  
Metastatic Activity ◽  
Hiv 1

Therapeutic DNA-vaccination against drug-resistant HIV-1 may hinder emergence and spread of drug-resistant HIV-1, allowing for longer successful antiretroviral treatment (ART) up-to relief of ART. We designed DNA-vaccines against drug-resistant HIV-1 based on consensus clade A integrase (IN) resistant to raltegravir: IN_in_r1 (L74M/E92Q/V151I/N155H/G163R) or IN_in_r2 (E138K/G140S/Q148K) carrying D64V abrogating IN activity. INs, overexpressed in mammalian cells from synthetic genes, were assessed for stability, route of proteolytic degradation, and ability to induce oxidative stress. Both were found safe in immunotoxicity tests in mice, with no inherent carcinogenicity: their expression did not enhance tumorigenic or metastatic potential of adenocarcinoma 4T1 cells. DNA-immunization of mice with INs induced potent multicytokine T-cell response mainly against aa 209–239, and moderate IgG response cross-recognizing diverse IN variants. DNA-immunization with IN_in_r1 protected 60% of mice from challenge with 4Tlluc2 cells expressing non-mutated IN, while DNA-immunization with IN_in_r2 protected only 20% of mice, although tumor cells expressed IN matching the immunogen. Tumor size inversely correlated with IN-specific IFN-γ/IL-2 T-cell response. IN-expressing tumors displayed compromised metastatic activity restricted to lungs with reduced metastases size. Protective potential of IN immunogens relied on their immunogenicity for CD8+ T-cells, dependent on proteasomal processing and low level of oxidative stress.

scholarly journals Erythrocyte-driven immunization via biomimicry of their natural antigen-presenting function

2020 ◽  
Vol 117 (30) ◽  
pp. 17727-17736 ◽  
Author(s):  
Anvay Ukidve ◽  
Zongmin Zhao ◽  
Alexandra Fehnel ◽  
Vinu Krishnan ◽  
Daniel C. Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Innate Immune ◽  
Effective Strategy ◽  
Number Density ◽  
Memory T Cell ◽  
Erythrocyte Surface ◽  
Antigen Presenting

Erythrocytes naturally capture certain bacterial pathogens in circulation, kill them through oxidative stress, and present them to the antigen-presenting cells (APCs) in the spleen. By leveraging this innate immune function of erythrocytes, we developed erythrocyte-driven immune targeting (EDIT), which presents nanoparticles from the surface of erythrocytes to the APCs in the spleen. Antigenic nanoparticles were adsorbed on the erythrocyte surface. By engineering the number density of adsorbed nanoparticles, (i.e., the number of nanoparticles loaded per erythrocyte), they were predominantly delivered to the spleen rather than lungs, which is conventionally the target of erythrocyte-mediated delivery systems. Presentation of erythrocyte-delivered nanoparticles to the spleen led to improved antibody response against the antigen, higher central memory T cell response, and lower regulatory T cell response, compared with controls. Enhanced immune response slowed down tumor progression in a prophylaxis model. These findings suggest that EDIT is an effective strategy to enhance systemic immunity.

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