scholarly journals CD47/SIRPα blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy

2020 ◽  
Vol 8 (2) ◽  
pp. e000905 ◽  
Author(s):  
Hongfei Wang ◽  
Yixuan Sun ◽  
Xiuman Zhou ◽  
Chunxia Chen ◽  
Ling Jiao ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Cell Response ◽  
Regulatory Protein ◽  
T Cell Response ◽  
Antitumor Effects ◽  
Pathogen Invasion

BackgroundImmunotherapy has achieved remarkable advances via a variety of strategies against tumor cells that evade immune surveillance. As important innate immune cells, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, resisting tumor cells and promoting adaptive immune response. CD47 is found to be overexpressed on tumor cells and act as a don’t eat me’ signal, which contributes to immune evasion. Macrophages mediated phagocytosis via blockade CD47/SIRPα (signal regulatory protein alpha) interaction was proved to induce effective antitumor immune response.MethodsA novel peptide pep-20, specifically targeting CD47 and blocking CD47/SIRPα interaction, was identified via high-throughput phage display library bio-panning. The capability to enhance the macrophage-mediated phagocytosis activities and antitumor effects of pep-20 were investigated. The mechanism of pep-20 to induce T-cell response was explored by ex vivo analysis and confirmed via macrophage depleting strategy. The structure-activity relationship and D-amino acid substitution of pep-20 were also studied. The antitumor effects and mechanism of a proteolysis resistant D-amino acid derivate pep-20-D12 combined with irradiation (IR) were also investigated.ResultsPep-20 showed remarkable enhancement of macrophage-mediated phagocytosis to both solid and hematologic tumor cells in vitro, and inhibited tumor growth in immune-competent tumor-bearing mice. Furthermore, pep-20 promoted macrophages to mobilize the antitumor T-cell response with minimal toxicity. Furthermore, systemic administration of the derivate pep-20-D12 showed robust synergistic antitumor efficacy in combination with IR.ConclusionIn summary, these results demonstrated that CD47/SIRPα blocking peptides, pep-20 and its derivate, could serve as promising candidates to promote macrophages-mediated phagocytosis and immune response in cancer immunotherapy.

scholarly journals Nano-Microparticle Platforms in Developing Next-Generation Vaccines

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 606
Author(s):  
Giuseppe Cappellano ◽  
Hugo Abreu ◽  
Chiara Casale ◽  
Umberto Dianzani ◽  
Annalisa Chiocchetti
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Response ◽  
Humoral Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Next Generation ◽  
Emerging Viruses ◽  
Whole Cells ◽  
Effector Functions

The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8+ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8+ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic.

scholarly journals The immune response against myelin basic protein in two strains of rat with different genetic capacity to develop experimental allergic encephalomyelitis.

1975 ◽  
Vol 141 (1) ◽  
pp. 72-81 ◽  
Author(s):  
D E McFarlin ◽  
S C Hsu ◽  
S B Slemenda ◽  
F C Chou ◽  
R F Kibler
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Experimental Allergic Encephalomyelitis ◽  
Cell Response ◽  
Basic Protein ◽  
T Cell Response ◽  
Skin Tests ◽  
Allergic Encephalomyelitis ◽  
Experimental Allergic

After challenge with guiena pig basic protein (GPBP) Lewis (Le) rats, which are homozygous for the immune response experimental allergic encephalomyelitis (Ir-EAE) gene, developed positive delayed skin tests against GPBP and the 43 residue encephalitogenic fragment (EF); in addition, Le rat lymph node cells (LNC) were stimulated and produced migration inhibitory factor (MIF) when incubated in vitro with these antigens. In contrast Brown Norway (BN) rats, which lack the Ir-EAE gene, did not develop delayed skin tests to EF and their LNC were not stimulated and did not produce MIF when incubated in vitro with EF. These observations indicate that the Ir-EAE gene controls a T-cell response against the EF. Le rats produced measurable anti-BP antibody by radioimmunoassay after primary challenge. Although no antibody was detectable in BN rats by radioimmunoassay, radioimmunoelectrophoresis indicated that a small amount of antibody was formed after primary immunization. After boosting intraperitoneally, both strains of rat exhibited a rise in anti-BP antibody; which was greater in Le rats. In both strains of rat the anti-BP antibody reacted with a portion of the molecule other than the EF. Since EF primarily evokes a T cell response, it is suggested that the EF portion of the BP molecule may contain a helper determinant in antibody production.

scholarly journals Concomitant Targeting of Tumor Cells and Induction of T-cell Response Synergizes to Effectively Inhibit Trastuzumab-Resistant Breast Cancer

2012 ◽  
Vol 72 (17) ◽  
pp. 4417-4428 ◽  
Author(s):  
Qingfei Wang ◽  
Shau-Hsuan Li ◽  
Hai Wang ◽  
Yi Xiao ◽  
Ozgur Sahin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Tumor Cells ◽  
Cell Response ◽  
T Cell Response

scholarly journals T-Cell Response to Human Papillomavirus Type 58 L1, E6, and E7 Peptides in Women with Cleared Infection, Cervical Intraepithelial Neoplasia, or Invasive Cancer

2010 ◽  
Vol 17 (9) ◽  
pp. 1315-1321 ◽  
Author(s):  
Paul K. S. Chan ◽  
Shih-Jen Liu ◽  
T. H. Cheung ◽  
Winnie Yeo ◽  
S. M. Ngai ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Amino Acid ◽  
T Cell ◽  
Cell Response ◽  
Positive Response ◽  
Intraepithelial Neoplasia ◽  
Amino Acid Position ◽  
T Cell Response ◽  
Ifn Γ ◽  
E6 And E7

ABSTRACT Human papillomavirus type 58 (HPV-58) exists in a relatively high prevalence in certain parts of the world, including East Asia. This study examined the T-cell response to HPV-58 L1, E6, and E7 peptides among women with cleared infection, cervical intraepithelial neoplasia grade 2 (CIN2) or CIN3, or invasive cervical cancer (ICC). Peptides found to be reactive in the in vitro peptide binding assay or mouse-stimulating study were tested with a gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay to detect peptide-specific responses from the peripheral blood mononuclear cells (PBMC) collected from 91 HPV-58-infected women (32 with cleared infection, 16 CIN2, 15 CIN3, and 28 ICC). Four HLA-A11-restricted HPV-58 L1 peptides, located at amino acid positions 296 to 304, 327 to 335, 101 to 109, and 469 to 477, showed positive IFN-γ ELISPOT results and were mainly from women with cleared infection. Two HLA-A11-restricted E6 peptides (amino acid positions 64 to 72 and 94 to 102) and three HLA-A11-restricted E7 peptides (amino acid positions 78 to 86, 74 to 82, and 88 to 96) showed a positive response. A response to E6 and E7 peptides was mainly observed from subjects with CIN2 or above. One HLA-A2-restricted E6 peptide, located at amino acid position 99 to 107, elicited a positive response in two CIN2 subjects. One HLA-A24-restricted L1 peptide, located at amino acid position 468 to 476, also elicited a positive response in two CIN2 subjects. In summary, this study has identified a few immunogenic epitopes for HPV-58 E6 and E7 proteins. It is worthwhile to further investigate whether responses to these epitopes have a role in clearing an established cervical lesion.

scholarly journals Neoantigen-specific CD4+ T-cell response is critical for the therapeutic efficacy of cryo-thermal therapy

2020 ◽  
Vol 8 (2) ◽  
pp. e000421
Author(s):  
Peng Peng ◽  
Hongming Hu ◽  
Ping Liu ◽  
Lisa X Xu
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Tumor Antigen ◽  
Cell Response ◽  
Antitumor Immunity ◽  
T Cell Response ◽  
Thermal Therapy ◽  
Term Survival

BackgroundTraditional tumor thermal ablations, such as radiofrequency ablation (RFA) and cryoablation, can result in good local control of tumor, but traditional tumor thermal ablations are limited by poor long-term survival due to the failure of control of distal metastasis. Our previous studies developed a novel cryo-thermal therapy to treat the B16F10 melanoma mouse model. Long-term survival and T-cell-mediated durable antitumor immunity were achieved after cryo-thermal therapy, but whether tumor antigen-specific T-cells were augmented by cryo-thermal therapy was not determined.MethodsThe long-term antitumor therapeutic efficacy of cryo-thermal therapy was performed in B16F10 murine melanoma models. Splenocytes derived from mice treated with RFA or cryo-thermal therapy were coincubated with tumor antigen peptides to detect the frequency of antigen specific CD4+ and CD8+ T-cells by flow cytometry. Splenocytes were then stimulated and expanded by αCD3 or peptides and adoptive T-cell therapy experiments were performed to identify the antitumor efficacy of T-cells induced by RFA and cryo-thermal therapy. Naïve mice and tumor-bearing mice were used as control groups.ResultsLocal cryo-thermal therapy generated a stronger systematic antitumor immune response than RFA and a long-lasting antitumor immunity that protected against tumor rechallenge. In vitro studies showed that the antigen-specific CD8+ T-cell response was induced by both cryo-thermal therapy and RFA, but the strong neoantigen-specific CD4+ T-cell response was only induced by cryo-thermal therapy. Cryo-thermal therapy-induced strong antitumor immune response was mainly mediated by CD4+ T-cells, particularly neoantigen-specific CD4+ T-cells.ConclusionCryo-thermal therapy induced a stronger and broader antigen-specific memory T-cells. Specifically, cryo-thermal therapy, but not RFA, led to a strong neoantigen-specific CD4+ T-cell response that mediated the resistance to tumor challenge.

Robust Anti‐Tumor T Cell Response with Efficient Intratumoral Infiltration by Nanodisc Cancer Immunotherapy

2020 ◽  
Vol 3 (9) ◽  
pp. 2000094 ◽  
Author(s):  
Rui Kuai ◽  
Priti B. Singh ◽  
Xiaoqi Sun ◽  
Cheng Xu ◽  
Alireza Hassani Najafabadi ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
Cell Response ◽  
T Cell Response

scholarly journals The Polyomavirus BK Large T-Antigen-Derived Peptide Elicits an HLA-DR Promiscuous and Polyfunctional CD4+T-Cell Response

2011 ◽  
Vol 18 (5) ◽  
pp. 815-824 ◽  
Author(s):  
Bala Ramaswami ◽  
Iulia Popescu ◽  
Camila Macedo ◽  
Chunqing Luo ◽  
Ron Shapiro ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
T Antigen ◽  
T Cell Response ◽  
Peptide Sequence ◽  
Large T Antigen ◽  
Hla Dr ◽  
Ifn Γ

ABSTRACTBK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4+T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4+T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.

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