General Principles of Tumor Immunotherapy: Basic and Clinical Applications of Tumor Immunology

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The fact that immunization with femtomole quantities of antigenic peptides chaperoned by HSPs is effective in eliciting such potent T cell responses is noteworthy By way of comparison, tens to hundreds of micrograms or tens of nanomoles of peptides in a conventional microbial adjuvant are typically used to immunize and elicit a similar response 47 , Further investigation was required to analyze how immunization with femtomoles of peptides is effective.

There is a general biological principle that extraordinary efficiencies are always achieved through specific receptors. PC, followed by the processing of peptides and their presentation by MHC molecules The subsequent investigations demonstrated this hypothesis and the answer to this conundrum was identified as CD Once HSP.

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PC is taken up through CD91, it may enter one or more of several trafficking and processing pathways, which are likely to lead to the stimulation of various T cell responses. PC with CD91 leads to the internalization of complexes into a non-acidic endosomal compartment and then the complex or the peptide alone is transferred to the cytosol 51 — 53 by an unknown mechanism. Next, the peptides are processed by the proteasomes and are transported into the ER by the transporters associated with antigen processing TAP The peptides are then loaded onto MHC class I molecules.

The occupied MHC molecules then pass through the secretory pathway to the cell surface where they interact with the receptors of CD8 T cells. Thus, HSP. CD91 is the main receptor involved in this HSP-based immune response, however, there may be other specific receptors involved, which are currently being investigated It is generally accepted that HSPs, functioning as chaperones for tumor antigens, elicit tumor-specific adaptive immune responses.

HSPs also appear to induce innate immune responses in an antigen-independent fashion.

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"General Principles of Tumor Immunotherapy: Basic and Clinical Applications of Tumor Immunology" brings together the world's leading authorities on tumor. Download Citation on ResearchGate | General principles of tumor immunotherapy: Basic and clinical applications of tumor immunology | Describes how the.

Innate responses generated by HSPs may contribute to antitumor immunity. Binder et al 60 previously confirmed that the immunization of mice with the HSP, gp96, but not the control proteins, leads to a 5—7 fold enlargement of the draining lymph nodes. The previously described immune responses associated with innate immune responses induced by HSPs have independent peptides and play a role in antitumor responses. Previous studies by Udono and Srivastava and Ciupitu et al confirmed that prophylactic vaccination with HSPs isolated from normal tissues cause complete tumor rejection in a small proportion of animals, in this case, tumor-specific T cells were not expected to be primed 37 , Baker-LePain et al demonstrated that the rate of tumor growth was slowed without causing complete tumor rejection by HSPs secreted from various irradiated tumor cells and fibroblast lines, in an antigen-non-specific manner In therapeutic settings, tumor-unrelated HSP preparations have been observed to reduce the metastatic burden and prolong the survival rate of mice, albeit in a significantly smaller percentage of mice compared with those treated with tumor-derived HSP preparations Collectively, while the innate immune response elicited by HSPs contributes to tumor immunity, the adaptive immune responses elicited by HSP-chaperoned tumor-specific peptides are more important in the antitumor immunity.

The two largest randomized, open-label, multicenter phase III clinical trials reported in further confirmed that HSP-based vaccines are safe, effective and clinically feasible, which inspires further research. Firstly, the immunogenicity is not strong enough, since the efficacy was usually observed in early-stage disease or with high-dose vaccination, which is consistent with the results obtained in mice. Therefore, the enhancement of the clinical effect is urgently required. To enhance the immunogenicity, specific new methods to prepare the vaccine have been developed, and improved antitumor immune responses have been observed 65 , This new vaccine may present an improved treatment against malignant cancer 67 , Tumor-derived HSP-based vaccines have shown great prospect in tumor immune therapy.

Various animal studies and clinical trials have demonstrated the efficacy, safety and feasibility of this vaccine. It is now clear that the immunogenicity entity was HSP-peptide complexes derived from tumors and the mechanism was due to activation of adaptive and innate immunity following the interaction of HSP. PC with APCs through receptor mediated endocytosis.

However, the limitations are also apparent: i the immunogenicity is not strong enough and ii the yield of tumor vaccine was limited. Certain alternatives to improve the vaccine have been made and enhanced responses have been observed.

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In the future, focus should be on how to improve the immunogenicity and how to increase the bioavailable efficiency of this vaccine. Tumor-derived HSP. PC-based vaccines are a promising vaccination strategy and are likely to provide great help to tumor patients. Ritossa P: Problems of prophylactic vaccinations of infants. Riv Ist Sieroter Ital.

Basic and Clinical Applications of Tumor Immunology

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Tumor Immunology and Immunotherapy

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Nat Immunol. Kojima T, Yamazaki K, Tamura Y, et al: Granulocyte-macrophage colony-stimulating factor gene-transduced tumor cells combined with tumor-derived gp96 inhibit tumor growth in mice. Hum Gene Ther.

General principles of tumor immunotherapy : basic and clinical applications of tumor immunology

Or get it by Thu, Sep 26 with faster delivery. PRC2 epigenetically silences Th1-type chemokines to suppress effector T-cell trafficking in colon cancer. In your cart, save the other item s for later in order to get NextDay delivery. Tang, H. Rosenbaum, L.

Cancer Immun. Srivastava P: Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol. J Leukoc Biol. Srivastava P: Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol. Berwin B and Nicchitta CV: To find the road traveled to tumor immunity: the trafficking itineraries of molecular chaperones in antigen-presenting cells.

Castelli C, Rivoltini L, Rini F, et al: Heat shock proteins: biological functions and clinical application as personalized vaccines for human cancer. Srivastava PK and Das MR: The serologically unique cell surface antigen of Zajdela ascitic hepatoma is also its tumor-associated transplantation antigen.

Cancer Immunotherapy

Int J Cancer. Hoos A and Levey DL: Vaccination with heat shock protein-peptide complexes: from basic science to clinical applications. Expert Rev Vaccines. Gross L: Intradermal immunization of C3H mice against a sarcoma that originated in an animal of the same line.

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J Natl Cancer Inst. Ann NY Acad Sci. Preprogram Course: Introduction to Immunology. Participation in this online preprogram course is strongly recommended as it contains information that will not be covered at the program on August This interactive course provides foundational knowledge that is necessary for understanding cancer immunotherapy content that will be discussed at the in-person program.

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