scholarly journals The Initial Immune Reaction to a New Tumor Antigen Is Always Stimulatory and Probably Necessary for the Tumor's Growth

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Richmond T. Prehn
Keyword(s):  
Tumor Growth ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
Immune Reaction ◽  
Mouse Skin ◽  
Initial Reaction ◽  
Adaptive Immune ◽  
Induced Tumors ◽  
Initial Effect ◽  
The Relationship

All nascent neoplasms probably elicit at least a weak immune reaction. However, the initial effect of the weak immune reaction on a nascent tumor is always stimulatory rather than inhibitory to tumor growth, assuming only that exposure to the tumor antigens did not antedate the initiation of the neoplasm (as may occur in some virally induced tumors). This conclusion derives from the observation that the relationship between the magnitude of an adaptive immune reaction and tumor growth is not linear but varies such that while large quantities of antitumor immune reactants tend to inhibit tumor growth, smaller quantities of the same reactants are, for unknown reasons, stimulatory. Any immune reaction must presumably be small before it can become large; hence the initial reaction to the first presentation of a tumor antigen must always be small and in the stimulatory portion of this nonlinear relationship. In mouse-skin carcinogenesis experiments it was found that premalignant papillomas were variously immunogenic, but that the carcinomas that arose in them were, presumably because of induced immune tolerance, nonimmunogenic in the animal of origin.

scholarly journals SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marta Ferreira-Gomes ◽  
Andrey Kruglov ◽  
Pawel Durek ◽  
Frederik Heinrich ◽  
Caroline Tizian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Immune Reaction ◽  
Adaptive Immune Response ◽  
Gene Expression Signature ◽  
Spike Protein ◽  
Single Cell Level ◽  
Cell Level ◽  
Adaptive Immune

AbstractThe pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.

scholarly journals Theragnostic Glycol Chitosan-Conjugated Gold Nanoparticles for Photoacoustic Imaging of Regional Lymph Nodes and Delivering Tumor Antigen to Lymph Nodes

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1700
Author(s):  
In-Cheol Sun ◽  
SeongHoon Jo ◽  
Diego Dumani ◽  
Wan Su Yun ◽  
Hong Yeol Yoon ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Immunotherapy ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
Imaging System ◽  
Superior Performance ◽  
Glycol Chitosan ◽  
Cervical Lymph Nodes

Lymph node mapping is important in cancer immunotherapy because the morphology of lymph nodes is one of the crucial evaluation criteria of immune responses. We developed new theragnostic glycol-chitosan-coated gold nanoparticles (GC-AuNPs), which highlighted lymph nodes in ultrasound-guided photoacoustic (US/PA) imaging. Moreover, the ovalbumin epitope was conjugated GC-AuNPs (OVA-GC-AuNPs) for delivering tumor antigen to lymph node resident macrophage. In vitro studies proved the vigorous endocytosis activity of J774A.1 macrophage and consequent strong photoacoustic signals from them. The macrophages also presented a tumor antigen when OVA-GC-AuNPs were used for cellular uptake. After the lingual injection of GC-AuNPs into healthy mice, cervical lymph nodes were visible in a US/PA imaging system with high contrast. Three-dimensional analysis of lymph nodes revealed that the accumulation of GC-AuNPs in the lymph node increased as the post-injection time passed. Histological analysis showed GC-AuNPs or OVA-GC-AuNPs located in subcapsular and medullar sinuses where macrophages are abundant. Our new theragnostic GC-AuNPs present a superior performance in US/PA imaging of lymph nodes without targeting moieties or complex surface modification. Simultaneously, GC-AuNPs were able to deliver tumor antigens to cause macrophages to present the OVA epitope at targeted lymph nodes, which would be valuable for cancer immunotherapy.

scholarly journals 769 A single dose of intratumoral TransCon™ TLR7/8 agonist monotherapy promoted sustained activation of antigen presenting cells resulting in CD4+ and CD8+ T cell activation and tumor growth inhibition

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A804-A804
Author(s):  
Luis Zuniga ◽  
Karan Uppal ◽  
Kathy Bang ◽  
Enping Hong ◽  
Simran Sabharwal ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Tumor Antigen ◽  
Tumor Growth Inhibition ◽  
Tlr Agonists ◽  
Syngeneic Mouse ◽  
Antigen Presenting ◽  
Anti Tumor Activity ◽  
Dose Dependent

BackgroundThe use of pattern recognition receptor agonists (PRRAs) such as Toll-like receptor (TLR) agonists is an attractive approach for cancer immunotherapy. TLR agonism elicits anti-tumor activity by activating antigen presenting cells (APCs) to promote a proinflammatory microenvironment and anti-tumor immunity. Local delivery of TLR agonists has shown encouraging preclinical and clinical anti-tumor benefit. However, intratumoral (IT) delivery of naked PRRAs may lead to rapid effusion from the tumor microenvironment, potentially impacting their effectiveness in inducing local inflammation and may promote systemic cytokine release, increasing the risk of adverse effects.MethodsTransConTM TLR7/8 Agonist was designed to address the current limitations of PRRA therapies and IT delivery through sustained and controlled release of resiquimod, a potent TLR7/8 agonist, following IT administration of a hydrogel depot.ResultsA single IT injection of TransCon TLR7/8 Agonist induced potent tumor growth inhibition in a dose-dependent manner in syngeneic mouse CT26 tumors. Following IT TransCon TLR7/8 Agonist treatment, acute and sustained upregulation of cell surface markers indicative of activation of APCs, such as CD54, CD69, and CD86, in the tumor was observed by fluorescence activated flow cytometry (FACs). Additionally, TransCon TLR7/8 Agonist treatment was associated with an increase in the frequency of APCs with an activated phenotype in tumor draining lymph nodes (LNs). Further, a concomitant potentiation in the frequency of activated CD4 and CD8 T cells in tumor draining LNs following IT TransCon TLR7/8 Agonist treatment was observed, as demonstrated by increased expression of Ki67, ICOS, or granzyme B.ConclusionsThese data support that a single IT dose of TransCon TLR7/8 Agonist can mediate robust anti-tumor activity as a monotherapy in the CT26 syngeneic mouse tumor model while promoting local activation of intratumoral APCs. Such activation may promote tumor antigen uptake and migration to tumor-associated lymphoid tissue, as evidenced by an increase in APCs with an activated phenotype in tumor draining LNs following TransCon TLR7/8 Agonist treatment. Activated tumor antigen-bearing APCs can promote the priming and activation of tumor-specific T cells in the tumor-draining LNs. Consistently, a dose-dependent increase in the frequency of T cells with an activated effector phenotype in tumor draining LNs following administration of TransCon TLR7/8 Agonist was observed. These preclinical data further support TransCon TLR7/8 Agonist as a novel and potentially efficacious PRRA therapy. A clinical trial to evaluate safety and efficacy of TransCon TLR7/8 Agonist as monotherapy, and in combination with pembrolizumab, in cancer patients has been initiated (transcendIT-101; NCT04799054).Ethics ApprovalThe animal studies performed described were performed in accordance with the “Guide for the Care and Use of Laboratory Animals: Eighth Edition” and approved by the institutional animal care and use committee (IACUC).

scholarly journals T cell suppressors of antitumor immunity. The production of Ly-1-,2+ suppressors of delayed sensitivity precedes the production of suppressors of protective immunity.

1986 ◽  
Vol 164 (4) ◽  
pp. 1179-1192 ◽  
Author(s):  
A DiGiacomo ◽  
R J North
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Antitumor Immunity ◽  
Tumor Antigens ◽  
Suppressor Cell ◽  
Passive Transfer ◽  
Concomitant Immunity ◽  
Adoptive Immunity ◽  
Suppressor T Lymphocytes ◽  
Early Tumor

The results of this study show that during growth of the immunogenic Meth A fibrosarcoma, two different types of suppressor T lymphocytes are generated in sequence. One type is generated during early tumor growth, reaches peak number around day 6, and is progressively lost thereafter. It is defined by its ability, upon passive transfer, to suppress the expression of a DTH reaction to tumor antigens in tumor-immunized recipients. It bears the Ly1-,2+ membrane phenotype and is sensitive to relatively low doses of cyclophosphamide. In contrast, the second type of suppressor cell is not detected until after day 9 of tumor growth, and is defined by its ability to inhibit, upon passive transfer, the expression of adoptive immunity against an established tumor in T cell-deficient recipients. According to previous studies it bears the Ly1+,2-, L3T4a+ membrane phenotype and is less sensitive to cyclophosphamide than the T cell suppressor of DTH. It is argued that this second type of suppressor T cell seems likely to be responsible for the escape of immunogenic tumors from antitumor immunity, because it can suppress the expression of a powerful mechanism of antitumor immunity in recipient mice, and is generated progressively as the tumor-bearing host loses concomitant immunity. In contrast, although the Ly-1-,2+ T cell suppressors of DTH can efficiently suppress a DTH reaction to an implant of living tumor cells, they fail to suppress the expression of immunity to the same implant.

Inhibición de Crecimiento de Tumores de Cáncer de Próstata en Hipertermia Magnética mediada por Nanopartículas en Estudios Preclínicos: una Revisión de Alcance

2021 ◽  
Author(s):  
◽  
J. A. Parada Peralta
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Magnetic Nanoparticle ◽  
Magnetic Hyperthermia ◽  
Tumor Growth Inhibition ◽  
Tissue Penetration ◽  
Deep Tissue ◽  
Incidence And Mortality ◽  
Low Toxicity ◽  
The Relationship

Prostate Cancer is one of the major concern types of cancer among men with respect to incidence and mortality. One relatively recent therapy against it, provided by Nanomedicine, is Nanoparticle mediated Magnetic Hyperthermia, which consists on tumor heating when exposed to an Alternating Magnetic Field in order to inhibit tumor growth (around 42 °C) (and make tumor sensible to other therapies: synergia) or to cause cancer cell apoptosis (greater temperature than 42°C). This procedure has several advantages like deep-tissue-penetration, targeted heating, low toxicity by Nanoparticles, and others. To this treatment, some of the Magnetic Nanoparticle properties are fundamental to its success, principaly the size, morphology, etc. Here, therefore, the relationship between the size of the employed Nanoparticles and the Tumor Growth Inhibition that cause is reviewed when treating Prostate Cancer tumors on mice models by Magnetic Hyperthermia.

scholarly journals Selective tumor antigen vaccine delivery to human CD169+antigen-presenting cells using ganglioside-liposomes

2020 ◽  
Vol 117 (44) ◽  
pp. 27528-27539
Author(s):  
Alsya J. Affandi ◽  
Joanna Grabowska ◽  
Katarzyna Olesek ◽  
Miguel Lopez Venegas ◽  
Arnaud Barbaria ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Dependent Manner ◽  
Cross Presentation ◽  
Vaccine Carrier ◽  
Antigen Presenting

Priming of CD8+T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14+CD169+monocytes and Axl+CD169+DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169+moDCs and Axl+CD169+DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8+T cells. Finally, Axl+CD169+DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169+DCs to drive antitumor T cell responses.

scholarly journals A nanoparticle vaccine that targets neoantigen peptides to lymphoid tissues elicits robust antitumor T cell responses

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Carlos A. Arbelaez ◽  
Juan Estrada ◽  
Melissa A. Gessner ◽  
Charles Glaus ◽  
Agnieszka B. Morales ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Tumor Antigens ◽  
T Cell Responses ◽  
Tumor Growth Inhibition ◽  
Lymphoid Tissues ◽  
Dependent Manner ◽  
Kras Mutations ◽  
Peptide Antigens ◽  
Cell Responses

AbstractCancer vaccines using synthetic long peptides (SLP) targeting tumor antigens have been tested in the clinic but the outcomes have been unimpressive, perhaps because these peptides elicit predominantly CD4+ T cell responses. We hypothesized that enhanced delivery of peptide antigens to, and uptake in, secondary lymphoid tissues should elicit more robust CD8+ and CD4+ T cell responses and improved anti-tumor responses. Here, we have designed SLP-containing cationic lipoplexes (SLP–Lpx) that improve delivery of peptides to myeloid cells in the spleen and lymphatics. Using the G12D KRAS mutations as neoantigens, we found that vaccination of mice with naked synthetic peptides harboring the G12D mutation with CpG adjuvant stimulated mainly CD4+ T cell responses with limited tumor growth inhibition. On the other hand, immunization with SLP–Lpx stimulated both CD4+ and CD8+ T cells and suppressed tumor growth in a CD8+ T cell-dependent manner. Combination of the SLP–Lpx vaccines with a checkpoint inhibitor led to profound growth suppression of established tumors. These studies suggest that preferential targeting of peptides derived from neoantigens to the spleen via lipoplexes elicits potent CD4+ and CD8+ T cell responses that inhibit tumor growth.

Immunoprotective Effect of Cu/Zn Superoxide Dismutase on Myeloid Graffi Tumor-Bearing Hamsters

2000 ◽  
Vol 55 (7-8) ◽  
pp. 649-656 ◽  
Author(s):  
Reneta A. Toshkova ◽  
Petia A. Dimitrova ◽  
Emilia H. Ivanova ◽  
Pavlina A. Dolashka ◽  
Maria B. Angelova ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Tumor Growth ◽  
Protective Effect ◽  
Phagocytic Activity ◽  
Tumor Antigens ◽  
Early Stage ◽  
Tumor Development ◽  
Peritoneal Macrophages ◽  
Tumor Bearing

Abstract Investigation on the immunoprotective activity of Cu/Zn superoxide dismutase from Humicola lutea 103 AL (HLSOD) in hamsters with transplanted myeloid tumor was performed. Survivability, tumor growth and tumor transplantability were followed. The immune status of tumor-bearing animals, injected with the optimal protective HLSOD dose, was examined during 27 days after tumor transplantation by the following parameters: (i) the number, migration and phagocytic activity of peritoneal macrophages, (ii) the phagocytic activity of blood polymorphonuclear leukocytes (PMNs), (iii) the responsibility in vitro of spleen lymphocytes to T and B cell mitogens. It was established that intraperitoneal inoculation of HLSOD produced a protective effect on the development of tumors. Elongation of the latent time for tumor appearance and inhibition of the tumor growth were observed. The decreased percentage of mortality in early stage of tumor progression was established. Immunological studies on tumor-bearing hamsters (TBH) induced a tem porary immunorestoring effect on the suppressed phagocytic activities of peritoneal macrophages and blood PMNs during the first 14 days of tumor development. Moreover, HLSOD showed an expressed stimulating effect on proliferative activity in vitro of spleen B lymphocytes from healthy and TBH as well. The immunorestoring and protective effect of the enzyme was probably due to improve of the oxidant-antioxidant balance in peritoneal phagocytes. The tem porary character of the effect can be explained with the interference of immunosuppressing factors produced by tumor tissue as well as by the presence of tumor antigens, tumor cells and antigen-antibody complexes in the circulation.

scholarly journals Orf Virus-Based Therapeutic Vaccine for Treatment of Papillomavirus-Induced Tumors

2020 ◽  
Vol 94 (15) ◽  
Author(s):  
M. Schneider ◽  
M. Müller ◽  
A. Yigitliler ◽  
J. Xi ◽  
C. Simon ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Therapeutic Efficacy ◽  
Tumor Regression ◽  
Therapeutic Vaccine ◽  
Tumor Burden ◽  
Orf Virus ◽  
Cottontail Rabbit ◽  
Induced Tumors ◽  
First Time ◽  
Complete Tumor

ABSTRACT Orf virus (ORFV) represents a suitable vector for the generation of efficient, prophylactic antiviral vaccines against different pathogens. The present study investigated for the first time the therapeutic application of ORFV vector-based vaccines against tumors induced by cottontail rabbit papillomavirus (CRPV). ORFV-CRPV recombinants were constructed expressing the early CRPV gene E1, E2, E7, or LE6. In two independent experiments we used in total 23 rabbits which were immunized with a mixture of the four ORFV-CRPV recombinants or empty ORFV vector as a control 5 weeks after the appearance of skin tumors. For the determination of the therapeutic efficacy, the subsequent growth of the tumors was recorded. In the first experiment, we could demonstrate that three immunizations of rabbits with high tumor burden with the combined four ORFV-CRPV recombinants resulted in significant growth retardation of the tumors compared to the control. A second experiment was performed to test the therapeutic effect of 5 doses of the combined vaccine in rabbits with a lower tumor burden than in nonimmunized rabbits. Tumor growth was significantly reduced after immunization, and one vaccinated rabbit even displayed complete tumor regression until the end of the observation period at 26 weeks. Results of delayed-type hypersensitivity (DTH) skin tests suggest the induction of a cellular immune response mediated by the ORFV-CRPV vaccine. The data presented show for the first time a therapeutic potential of the ORFV vector platform and encourage further studies for the development of a therapeutic vaccine against virus-induced tumors. IMPORTANCE Viral vectors are widely used for the development of therapeutic vaccines for the treatment of tumors. In our study we have used Orf virus (ORFV) strain D1701-V for the generation of recombinant vaccines expressing cottontail rabbit papillomavirus (CRPV) early proteins E1, E2, LE6, and E7. The therapeutic efficacy of the ORFV-CRPV vaccines was evaluated in two independent experiments using the outbred CRPV rabbit model. In both experiments the immunization achieved significant suppression of tumor growth. In total, 84.6% of all outbred animals benefited from the ORFV-CRPV vaccination, showing reduction in tumor size and significant tumor growth inhibition, including one animal with complete tumor regression without recurrence.

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