scholarly journals An Evidence-based Medical Research on the Comparative Quantification of TGF? and Telomerase Experimentations, with their Molecular Pharmacological Analyses as Targets of Oncoimmunotherapeutic Vaccines

2021 ◽  
Vol 71 (2) ◽  
Author(s):  
Dr. Moumita Hazra
Keyword(s):  
T Cells ◽  
Medical Research ◽  
Evidence Based ◽  
Therapeutic Vaccines ◽  
Pharmacological Targets ◽  
Dendritic Cell Vaccines ◽  
Specific Antigens ◽  
Case Presentations ◽  
Antigen Presenting ◽  
Record Review

The basic oncotherapeutic vaccines used are cell based vaccines including whole cell vaccines, genetically modified tumour cell vaccines and dendritic cell vaccines, anti-idiotype antibody based vaccines, protein or peptide based vaccines, heat shock proteinbased vaccines, viral, bacterial or yeast vectors based vaccines, mRNA or DNA nucleic acid based vaccines, vaccines based on tumour associated antigens like overexpressed proteins, differentiation antigens, cancer-testis antigens and oncofoetal antigens, and tumour specific antigens including oncogenic viral antigens, antigen presenting cells or molecular neoantigens based vaccines with specific CD8+ T cells and, CD4+ T cells, and nanoparticles vectors based vaccines. The objective of this evidence-based medical research was the comparative quantification of TGF? and telomerase experimentations, with their molecular pharmacological analyses as targets of oncoimmunotherapeutic vaccines. A molecular pharmacological multi-variate, qualitative, analytical study of the retrieved literature derived through a thorough literature review from various available literature databases, was performed, to record, review, thoroughly analyse and delineate the molecular pharmacological basis of oncoimmunotherapeutic vaccines from a wide-ranged study literature containing molecular pharmacological researches, reviews, case presentations and varied databases about the pharmacooncoimmunotherapeutic rationale of the clinical use of vaccines in the treatment of cancer patients, with a specific emphasis on telomerase and TGF?, as molecular pharmacological targets of oncoimmunotherapeutic vaccines. After that, a multivariate evidence-based medical research study of comparative quantification and analysis of the global heterogenous multidisciplinary experimentations and study literature on telomerase and TGF?, as molecular pharmacological targets of pharmaco-oncoimmuno-therapeutic vaccines, affecting global malignant and borderline malign

Cross-Presentation by Host CD8α+dendritic Cells Augments Graft-Versus-Tumor Effect without Aggravating Graft-Versus-Host Disease After Allogeneic BMT

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 310-310
Author(s):  
Tomomi Toubai ◽  
Yaping Sun ◽  
Isao Tawara ◽  
Chen Liu ◽  
Pavan Reddy
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Conflicts Of Interest ◽  
Clinical Severity ◽  
Poly I:C ◽  
Cross Presentation ◽  
Target Organs ◽  
Specific Antigens ◽  
Similar Survival ◽  
Antigen Presenting

Abstract Abstract 310 Host hematopoietic derived antigen presenting cells (APCs) play an important role in the induction of GVHD and GVT. While all of the host hematopoietic derived APCs express and directly present allo-antigens that drive GVHD and GVT responses, the tumor specific antigens (TSA) expressed only on the tumor cells but not on the host professional APCs. TSAs will therefore need to be cross-presented on host hematopoietic derived APCs to generate optimal tumor antigen specific GVT response. We therefore reasoned that absence of cross-presentation by host hematopoietic derived professional APCs will not affect allo-antigen driven GVHD severity but may reduce GVT driven by TSAs. Because cross-presentation of antigens is mediated primarily by CD8α+dendritic cell (DCs) subset, we hypothesized that that cross-presentation by host CD8α+DCs will be critical for optimal GVT without aggravating GVHD. We utilized wild type (WT) B6 and B6 Batf3−/− animals (that lack the CD8α+ DCs) as recipients in well characterized MHC matched, minor mismatched C3H.SW “type=”#_x0000_t75”>B6 model of acute GVHD. WT and Batf3−/− animals received 10 Gy and were transplanted with 5 × 105 purified splenic CD8+T cells and 5 × 106 BM from either syngeneic B6 or allogeneic C3H.SW donors. Consistent with the hypothesis, the WT and the Batf3−/− animals showed similar survival and clinical severity of GVHD (P = NS). The increase in mortality was associated with a significant increase in the histopathological damage of the GVHD target organs (liver and intestine). Next, to determine the effect of host CD8α DCs on GVT responses, WT and Batf3−/−mice were conditioned and transplanted as above with syngeneic B6 or the C3H.sw donors along with 2×104MBL-2 tumor cells (which syngeneic to the host and express TSAs in addition to the allo-antigens that can be recognized by the donor T cells). All of the allogeneic WT and Batf3−/− mice developed GVHD. However, while none (0%) of the WT B6 animals died with tumor, 80% of the Batf3 KO mice had tumors at death (P<0.01, see Table). When the tumor dose was increased over two folds, 40% of the allogeneic WT animals died with tumor while 100% of the Batf3 KO animals died with tumors (P<0.05, see Table). Similar results were obtained with different tumor (EL-4) and GVHD (BALB/c→B6) models ruling tumor and strain dependent artifacts. Because toll-like receptor 3 (TLR-3) is primarily, but not exclusively, expressed on CD8α+DC subsets and has also been implicated in cross-presentation, to further confirm the relevance of cross-presentation by host APC subsets in mediating GVT, we generated [WT-B6→B6Ly5.2] and [TLR3−/−B6→B6Ly5.2] chimeras and utilized them as allo-recipients along with or without 5×105 MBL-2 tumor cells. All of the allogeneic [WT-B6→B6Ly5.2] and [TLR3−/−B6→B6Ly5.2] animals demonstrated similar GVHD. However, while only 50% of allogeneic [WT-B6→B6 Ly5.2] animals died with tumor, 100% of allogeneic [TLR3−/−→B6Ly5.2] animals died with tumor (P<0.05). To further confirm the specificity of TLR-3 and to determine whether GVT effect can be augmented by enhancing cross-presentation, we treated the chimeras with either poly I:C (which is a TLR-3 specific ligand and shown to promote cross-presentation) at 50μg/mice (day 0 and 1) or diluent control along with the MBL2-tumors after allo-BMT. Treatment with poly I:C reduced tumor induced mortality in the allogeneic [WT-B6→B6 Ly5.2] animals (50% vs. 8%, P<0.01, see Table), but did not alter tumor induced death in the [TLR3−/−→B6 Ly5.2] animals (100% vs. 93%, P=NS). Collectively, these data demonstrate, for the first time to our knowledge, that modulating antigen presentation on host APC (CD8α+ DC) subsets can augment GVT without aggravating GVHD. DonorRecipient (n)Tumor (dose)Mortality from relapseB6B6 WTMBL-2 (0.2×105)100%C3H.swB6 WTMBL-2 (0.2×105)0%**C3H.swBatf3−/−MBL-2 (0.2×105)80%C3H.swB6 WTMBL-2 (0.5×105)40%*C3H.swBatf3−/−MBL-2 (0.5×105)100%C3H.sw[B6 WTàB6Ly5.2]MBL-2 (0.5×105)50%**C3H.sw[TLR3−/−à B6Ly5.2]MBL-2 (0.5×105)100%C3H.sw[B6 WTàB6Ly5.2] +PolyI:CMBL-2 (0.5×105)8%***C3H.sw[TLR3−/−àB6Ly5.2] +PolyI:CMBL-2 (0.5×105)93%*P<0.05,**P<0.01,***p<0.001 Disclosures: No relevant conflicts of interest to declare.

Characterization of HLA-A*0201 restricted cytotoxic CD8+ T cells directed against ewing tumor specific antigens

2009 ◽  
Vol 221 (03) ◽  
Author(s):  
S Pirson ◽  
U Thiel ◽  
H Bernhard ◽  
GHS Richter ◽  
S Burdach
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Specific Antigens ◽  
Ewing Tumor

Critical contribution from antigen presenting cells for encephalitogenic T cells

2014 ◽  
Vol 275 (1-2) ◽  
pp. 65-66
Author(s):  
Priscilla Lee ◽  
Alan Smith ◽  
Yuhong Yang ◽  
Amanda Selhorst ◽  
Michael Racke ◽  
...  
Keyword(s):  
T Cells ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

scholarly journals OX40L–OX40 Signaling in Atopic Dermatitis

2021 ◽  
Vol 10 (12) ◽  
pp. 2578
Author(s):  
Masutaka Furue ◽  
Mihoko Furue
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Memory T Cells ◽  
Effector Memory ◽  
T Helper ◽  
T Helper 1 ◽  
Therapeutic Success ◽  
T Helper 2 ◽  
Promising Target ◽  
Antigen Presenting

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.

Interferon-γ-stimulated marrow stromal cells: a new type of nonhematopoietic antigen-presenting cell

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2570-2577 ◽  
Author(s):  
John Stagg ◽  
Sandra Pommey ◽  
Nicoletta Eliopoulos ◽  
Jacques Galipeau
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Stromal Cells ◽  
Matrix Protein ◽  
Marrow Stromal Cells ◽  
Human Mscs ◽  
Dependent Manner ◽  
Antigen Presenting ◽  
Significant Production

AbstractSeveral studies have demonstrated that marrow stromal cells (MSCs) can suppress allogeneic T-cell responses. However, the effect of MSCs on syngeneic immune responses has been largely overlooked. We describe here that primary MSCs derived from C57BL/6 mice behave as conditional antigen-presenting cells (APCs) and can induce antigen-specific protective immunity. Interferon gamma (IFNγ)-treated C57BL/6 MSCs, but not unstimulated MSCs, cocultured with ovalbumin-specific major histocompatibility (MHC) class II-restricted hybridomas in the presence of soluble ovalbumin-induced significant production of interleukin-2 (IL-2) in an antigen dose-dependent manner (P < .005). IFNγ-treated MSCs could further activate in vitro ovalbumin-specific primary transgenic CD4+ T cells. C57BL/6 MSCs, however, were unable to induce antigen cross-presentation via the MHC class I pathway. When syngeneic mice were immunized intraperitoneally with ovalbumin-pulsed IFNγ-treated MSCs, they developed antigen-specific cytotoxic CD8+ T cells and became fully protected (10 of 10 mice) against ovalbumin-expressing E.G7 tumors. Human MSCs were also studied for antigen-presenting functions. IFNγ-treated DR1-positive human MSCs, but not unstimulated human MSCs, induced significant production of IL-2 when cocultured with DR1-restricted influenza-specific humanized T-cell hybridomas in the presence of purified influenza matrix protein 1. Taken together, our data strongly suggest that MSCs behave as conditional APCs in syngeneic immune responses. (Blood. 2006;107:2570-2577)

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