Download or read book Cancer Immunotherapy written by Richard A. Morgan and published by Elsevier Inc. Chapters. This book was released on 2013-06-04 with total page 28 pages. Available in PDF, EPUB and Kindle. Book excerpt: Adoptive cell therapy for cancer using tumor antigen-reactive cytotoxic lymphocytes or with tumor infiltrating lymphocytes has been shown to be a potent therapy for metastatic cancer. The generation of tumor-reactive T cells is not always possible in all of the patients. To overcome this limitation, investigators can now insert highly avid T-cell receptors (TCR) into T cells that can recognize tumor antigens. Genetic engineering of TCR genes into normal T cells is a powerful new strategy to generate large numbers of defined antigen-specific cells for therapeutic application. This approach has evolved beyond experimental stage into a clinical reality. The feasibility of TCR engineered T cells has been shown to be an effective clinical strategy resulting in the regression of established tumors in recent clinical trials. In this chapter, the progress and prospects of TCR engineered T cells as a therapeutic strategy for treating patients with cancer are discussed.
Download or read book New Strategy for the Redirection of Cytolytic T Lymphocytes to Prostate Tumors written by and published by . This book was released on 1999 with total page 43 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our group has developed a model immunotherapy system using a chimeric T cell receptors to redirect cytotoxic T cells to tumors. The efficacy of this approach in reducing tumor burden has been demonstrated using our constructs in models of ovarian carcinoma. To apply this technology to prostate tumors, we will alter the specificity of patient-derived lymphocytes through stable modification with chimeric receptor genes consisting of a targeting molecule linked to a T cell activation molecule (the y subunit common to the Fc receptors, CD28 co-stimulatory receptor or Syk kinase). We have cloned, expressed, and immunized mice with two antigens expressed specifically on a large proportion of prostate tumors. These immunized mice will be used to produce prostate-specific monoclonal antibodies from which the scFv will be prepared. In addition, we have produced retroviruses capable of transducing human PBL with a chimeric receptor gene. Three targeting molecules have been used. We demonstrated their efficacy and the ability of the transduced lymphocytes to kill a prostate carcinoma line, LNCaP. We have started to put these constructs into lentiviral vectors which have the ability to transduce non- replicating cells. This therapeutic strategy may allow new approaches towards the adoptive immunotherapy of prostate cancer in humans.
Download or read book Prostate Cancer Immunotherapy Development in Prostate Specific Antigen Transgenic Mice written by and published by . This book was released on 1999 with total page 16 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our research is focused towards the development of an immunotherapy for prostate cancer that specifically targets the expressed prostate specific antigen (PSA) of prostate tumor cells. With over forty thousand deaths a year and the near lack of curative treatments, an effective therapy would greatly benefit society. Our research to date has suggested that PSA can serve as a tumor rejection marker in our PSA transgenic mice whose prostates express human PSA. Vaccination with a tumor cell that expresses PSA elicited a specific anti-PSA response that prevented the outgrowth of a tumor challenge of PSA expressing cells. After indicating the pertinence of PSA as a target of an immunotherapy, we attempted to identify PSA derived peptides that are immunogenic in the HLA-A0̂20l haplotype. Of nine PSA peptides selected for our study based on binding studies, two have proven to be immunogenic in the HLA- A0̂2O1/Dd transgenic mouse model after vaccination of peptide pulsed dendritic cells. These results indicate that not only can we use PSA as a plausible rejection marker but we can also elicit a CTL response directed against the human PSA peptides in a HLA-A0̂20l/Dd transgenic mouse. These results allow us to experiment with our vaccination strategies for the development of an efficacious anti-prostate cancer immunotherapy.
Download or read book Rescuing High Avidity T Cells for Prostate Cancer Immunotherapy written by and published by . This book was released on 2004 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is the first annual report on the grant Rescuing high avidity T cells for prostate cancer immunotherapy". The purpose of the grant proposal is to rescue high avidity tumor-antigen specific T cells that can respond effectively to prostate cancer cells and delay the development of prostate cancer in the TRAMP mouse model. The innovative idea is based on the hypothesis that blockade of the T cell costimulatory pathway in adults will inhibit the deletion of high avidity tumor antigen specific T cells. We have proposed three specific aims in the grant, (I) - Identify the cells in thymus that express peripheral tumor antigen to induce clonal deletion of tumor antigen reactive T cells. (2). Examine whether anti-B7 antibody treatment in TRAMP mice can rescue the tumor-antigen specific T cells that are otherwise deleted. (3). Determine the thymic function in prostate cancer patients undergoing hormonal therapy. In the past funding period, we have completed the specific aim 1 and obtained promising preliminary data in specific aim 2. Through bone marrow radiation chimera mice experiments that we proposed in specific aim 1, we have shown that expression of the self antigen in thymic epithelial cells is both necessary and sufficient to induce clonal deletion. Surprisingly, while bone marrow-derived peripheral antigen expressing cells failed to induce clonal deletion, they did cause the activation-induced cell death of autoreactive cells in the secondary lymphoid organs. Thus, the BM-derived PAE have a distinct function in the maintenance of tolerance to tissue-specific antigens.
Download or read book Vaccines for Cancer Immunotherapy written by Nima Rezaei and published by Academic Press. This book was released on 2018-10-17 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: Therapeutic cancer vaccines represent a type of active cancer immunotherapy. Clinicians, scientists, and researchers working on cancer treatment require evidence-based and up-to-date resources relating to therapeutic cancer vaccines. Vaccines for Cancer Immunotherapy provides a reference for cancer treatment for clinicians and presents a well-organized resource for determining high-potential research areas. The book considers that this promising modality can be made more feasible as a treatment for cancer. Chapters cover cancer immunology, general approaches to cancer immunotherapy, vaccines, tumor antigens, the strategy of allogeneic and autologous cancer vaccines, personalized vaccines, whole-tumor antigen vaccines, protein and peptide vaccines, dendritic cell vaccines, genetic vaccines, candidate cancers for vaccination, obstacles to developing therapeutic cancer vaccines, combination therapy, future perspectives and concluding remarks on therapeutic cancer vaccines. - Introduces the feasible immunotherapeutic vaccines for patients with different types of cancer - Presents the status of past and current vaccines for cancer treatment - Considers advantages and disadvantages of different therapeutic cancer vaccines - Looks at the combination of vaccines and other modalities, including immunotherapeutic and conventional methods - Analyzes obstacles to development of therapeutic cancer vaccines - Gives a view on future perspectives in the application of therapeutic cancer vaccines
Download or read book Development of Artificial Antigen Presenting Cells for Prostate Cancer Immunotherapy written by and published by . This book was released on 2004 with total page 10 pages. Available in PDF, EPUB and Kindle. Book excerpt: A major goal in cancer immunotherapy is to generate an effective anti-tumor immune response. Adoptive immunotherapy involves stimulation of tumor-specific T cells, ex vivo (outside the body), followed by transfer of expanded numbers of activated T cells back into patients. While adoptive immunotherapy holds promise as a treatment for cancer, development of adoptive immunotherapy has been impeded by the lack of a reproducible and economically viable method for generating therapeutic numbers of antigen-specific CTL. The work proposed in this application will enable advances in adoptive immunotherapy. Most prostate cancers express prostate specific molecules. These molecules, including PSA and PMSA, can serve as potential targets for immune-based treatments. Studies on immune recognition of these molecules have already identified potential target regions within these proteins and are the basis of a variety of different experimental immunotherapies for treatment of prostate cancer. In this study we propose to study the ability to use HLA-Ig based aAPC as a viable method for induction, expansion and activation of prostate specific T cells for immunotherapy for prostate cancer. These studies will serve as precursor ones for induction and expansion of prostate specific CTL from patients with disease for initiation of adoptive immunotherapy phase I clinical studies.
Download or read book Modulation of T Cell Tolerance in a Murine Model for Immunotherapy of Prostatic Adenocarcinoma Addendum written by and published by . This book was released on 2007 with total page 11 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of this project is to characterize T cell tolerance to prostate tumor antigens and to identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. We use the TRAMP model a transgenic mouse line that develops primary prostatic tumors due to expression of the SV40 T antigen (TAg) under the transcriptional control of a prostate-specific promoter. In this final addendum summary we report that subsequent to adoptive transfer of naive TAg-specific T cells into TRAMP mice there is rapid expansion and contraction of the tumor-specific T cells followed by accumulation of a population of T cells that persist in the prostate as tolerant and suppressive. Co-transfer of TAg-specific CD4+ T cells delays the tolerant suppressive phenotype of prostate-tumor-specific T cells. Transfer of CD4+ T cells does not reverse tolerance of previously-tolerized CD8+ cells. The suppressive nature of these CD8+ T cells was also studied and we demonstrate that suppression is at least in-part mediated by secreted factors. Further we demonstrate that trafficking od T cells to the TRAMP prostate may be mediated by chemokines. These data demonstrate the critical balance between T cell activation and tolerance and support a mechanism by which tumor growth may induce tolerance and suppressor activity in T cells previously primed to tumor-specific antigens. A greater understanding of how tolerance of these tumor specific T cells can be reversed will certainly lead to more potent anti-tumor immunotherapies.
Download or read book Immune Memory and Vaccines Great Debates written by Shane Crotty and published by Perspectives Cshl. This book was released on 2018-01-31 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: "A subject collection from the Cold Spring Harbor perspectives in biology."
Download or read book Modulation of T Cell Tolerance in a Murine Model for Immunotherapy of Prostatic Adenocarcinoma written by and published by . This book was released on 2004 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The goal of this project is to characterize T cell tolerance to prostate tumor antigens and identify the role of costimulatory receptors in overcoming this tolerance. Identification of these processes will assist in the development of novel therapeutic approaches for treating prostate cancer. We use the TRAMP model, a transgenic mouse line that develops primary prostatic tumors due to expression of the SV4O T antigen (TAg) under the transcriptional control of a prostate-specific promoter. In this summary, we report that adoptive transfer of naive TAg-specific T cells into TRAMP mice results in an initial proliferative expansion followed by a clonal deletion within 5 days. Vaccination of mice with dendritic cells pulsed with the cognate antigen results in expansion in the peripheral lymphoid compartments and subsequent trafficking to the Prostate-draining lymph nodes (pDLN). However, 11 days post-vaccine, Ag-specific T cells were no longer detectable in pDLN. In contrast, a large percentage of Ag-specific T cells were still present in the prostatic tissue of vaccinated TRAMP mice, and persisted for at least 21 days. These data demonstrate that an Ag-pulsed DC vaccine may "rescue" prostate-specific T cells from peripheral tolerance in tumor-bearing mice and promote their infiltration and survival in the prostate. On going studies are testing the role of CTLA-4 blockade and CD4+ T cell help to rescue this deletion.
Download or read book Cancer Immunotherapies written by Priya Hays and published by Springer Nature. This book was released on 2022-05-12 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents the clinical scope of cancer immunotherapeutic agents for solid tumors and Hematologic malignancies, elaborates on the scientific details of their modes of action, and presents the impact of these agents on oncology, patients and the broader healthcare system. At present, cancer immunotherapies fall broadly into three categories: immune checkpoint inhibitors (ICIs), adoptive T cell therapies, and cancer vaccines which have distinct mechanisms of action. Immune checkpoint inhibitors rely upon disrupting tumor antigen recognition as self by the immune system through inhibition of checkpoint molecules. Adoptive T cell therapies involve the engineering of T cells ex vivo to target and destroy tumor cells. The first part of this book will provide an overview of the discovery and mechanistic details of the technology. The second part will be devoted to elaborating on the clinical outcomes, successes and limitations for specific tumor subtypes, which includes both solid tumors and hematologic malignances for both pediatric and adult populations. As such, the book offers a valuable resource for oncologists, hematologists, and all those seeking an up-to-date overview of cancer immunotherapies.
Download or read book Development of Immunotherapy Against Prostate Cancer Using Lentivirally transduced Dendritic Cells Expressing Murine ErbB2 as a Model Tumor associated Antigen written by Miriam Esmat Mossoba and published by . This book was released on 2008 with total page 314 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer is a leading cause of cancer deaths in North American men. Current treatments are often not curative, particularly in cases of advanced metastatic disease. Immunotherapy is a promising approach to treating cancer as it harnesses the immune system's ability to mount potent responses against tumor-associated antigens (TAAs). Dendritic cells (DCs) play a central role in mediating antigen-specific immunity and have been recently used with some success in clinical trials. The difficulties associated with obtaining sufficient quantities of DCs from cancer patients provided the rationale for developing low-dose DC-based immunotherapy approaches in my thesis project. DCs were genetically engineered using a lentiviral vector (LV) to express erbB2tr, a kinase-deficient version of erbB2. The human form of erbB2, HER2/neu, is overexpressed in 20% of primary prostate tumors and 80% of their metastases, making this TAA an attractive target. Using this LV system, efficient transgene delivery into DCs was achieved without compromising DC function or phenotype. Administering low prime and boost doses (2x105 or 2x10 3) of LV-transduced DCs to mice yielded potent and long-term anti-tumor responses against murine prostate tumors engineered to overexpress erbB2tr. The 2x105 DC dose yielded complete tumor protection and was associated with humoral and cellular responses. The 2x10 3 dose also offered complete protection in some mice, ii suggesting that we had reached a lower threshold DC dose. This novel finding prompted us to determine if co-transducing DCs with an additional LV carrying the cDNA for an immunomodulatory factor could augment the efficacy of our low-dose strategy. We chose to test both the DC survival-enhancing RANKL protein and DC function-enhancing IL-12 in combination with erbB2tr. Although DCs co-transduced with the LV/RANKL and LV/erbB2tr did not appear to offer enhanced anti-tumor benefits in a prophylactic setting, co-transduction with LV/IL-12 and LV/erbB2tr did. The incorporation of IL-12 into the low-dose immunization strategy led to robust long-term tumor protection and relatively high levels of Th1 immunity. This is the first demonstration of the efficacy of low-dose DC-mediated immunotherapy using lentiviral vectors as gene transfer tools. These studies establish a platform for DC-mediated therapies that can be realistically translated to the clinic.
Download or read book Cancer Vaccines and Immunotherapy written by Peter L. Stern and published by Cambridge University Press. This book was released on 2000-08-17 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rapid progress in the definition of tumor antigens, and improved immunization methods, bring effective cancer vaccines within reach. In this wide-ranging survey, leading clinicians and scientists review therapeutic cancer vaccine strategies against a variety of diseases and molecular targets. Intended for an interdisciplinary readership, their contributions cover the rationale, development, and implementation of vaccines in human cancer treatment, with specific reference to cancer of the cervix, breast, colon, bladder, and prostate, and to melanoma and lymphoma. They review target identification, delivery vectors and clinical trial design. The book begins and ends with lucid overviews from the editors, that discuss the most recent developments.
Download or read book Chimeric Antigen Receptor Engineered T Cells for Adoptive Immunotherapy of Prostate Cancer written by Gaia Zuccolotto and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Developments in T Cell Based Cancer Immunotherapies written by Paolo A. Ascierto and published by Humana Press. This book was released on 2015-11-26 with total page 315 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume illustrates the salient aspects of cancer biology relevant to the successful implementation of immunotherapy. Topics include enhancement of antigen-specific immune responses by anti-cancer vaccines, modulation of the function of T cells within the tumor microenvironment, and the effects of genetic, epigenetic, developmental, and environmental determinants on T cell function. Other topics covered include the ex vivo expansion of T or other immune cells and their genetic modification or reprogramming to increase their ability to survive and expand when adoptively transferred back to the patients. Specific attention is devoted to the genetic manipulation of T cells through the introduction of re-directed T cell receptors, chimeric antibody receptors, and other genetic manipulation aimed at improving their effectiveness as anti-cancer agents. Furthermore, the revolutionary role of checkpoint inhibitors and their potential in combination with other immunotherapeutic approaches or with standard chemo and radiation therapy are extensively discussed.
Download or read book Construction Optimization and Application of Hsp72 conjugate Tumor Antigen Vaccines written by Matthew John Kelly and published by . This book was released on 2017 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: Prostate cancer and melanoma remain significant contributors to cancer-related mortality. The metastatic forms of these cancers are particularly deadly, with 5-year survival estimates of 29% for prostate cancer and 15-20% for melanoma. One of the promising treatment strategies for these deadly diseases is active immunotherapy, better known as vaccination. Recent FDA approval of the first active immunotherapy for the treatment of metastatic castrate-resistant prostate cancer supports the relevance of continued cancer vaccine research. Cancer vaccines stimulate the patient's immune system to target tumor or tissue-specific antigens, resulting in elimination of cells expressing these antigens. Importantly, many tumor or tissue-specific targets have been described, such as prostatic acid phosphatase (PAP) in prostate cancer and gp100 in melanoma. However, previous applications of these antigens in clinical vaccination studies have largely failed to elicit robust antigen-specific immune responses. Therefore, the need exists for strategies to increase the immunogenicity of active immunotherapy strategies for the treatment of prostate cancer and melanoma. Inclusion of the immunostimulatory heat shock protein 72 (Hsp72) in active immunotherapeutic strategies may serve to increase the immunogenicity of these vaccines. We've found that DNA vaccines encoding fusion proteins of Hsp72, and either gp100 or PAP, potentiate immunogenicity of transfected cells via overexpression of the proteins of interest, and increased cell-surface MHC class I expression. Furthermore, in a mouse melanoma model, we found that application of cellular vaccines that overexpressed Hsp72 and gp100 proteins delayed tumor progression upon challenge. Additionally, we found that DNA and cellular vaccines expressing fusion proteins of Hsp72 and PAP were capable of eliciting PAP-specific immune responses in vaccinated mice. Overall, these studies demonstrate that DNA and cellular vaccines employing Hsp72-conjugation are immunostimulatory, and represent a strategy to enhance the efficacy of antitumor active immunotherapies.
Download or read book Enhancement of T Cell Responses Through CTLA 4 Blockade Combination Therapy in a Mouse Model of Prostate Cancer written by Rebecca Waitz and published by . This book was released on 2008 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Proto Oncogene PML and Tumor Evasion in Prostate Cancer written by and published by . This book was released on 2000 with total page 122 pages. Available in PDF, EPUB and Kindle. Book excerpt: The peptides presented by class I human leukocyte antigen (HLA) are the primary targets on tumor cells for immune recognition by host cytotoxic T lymphocytes (CTL). Tumors can therefore avoid CTL recognition by down-regulation of cell surface HLA. However, the molecular mechanism of HLA down-regulation and its significance in progression of prostate carcinoma have not been determined. We have proposed to identify the antigen presentation defects in prostate cancer, to examine the role of proto-oncogene PML in HLA class I down regulation in prostate cancer, and to study the immune regulation in experimental transgenic murine prostate cancer (TRAMP) models. In the past funding period, we have performed immunohistochemical study to show the concordant proto-oncogene PML and HLA class I antigen down-regulation in surgically removed prostate cancer lesions We have examined the proto-oncogene PML isoform expression and antigen presentation gene expression in prostate cancer cell lines. Most importantly, we made the important discovery that thymic deletion is the major mechanism of T cell immune tolerance in TRAMP mouse model. We believe that these works will open new revenues for prostate cancer immunotherapy.
