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At least 163 records · Page 9Linked to original sources
PubMed2005

Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin/ML-IAP in lung cancer.

CD8(+) CTLs have an essential role in immune response against tumor. Although an increasing number of tumor-associated antigens that can be recognized by CTLs have been identified from human tumors, a limited number of tumor-associated antigens is known in lung cancer. In addition, because some of them are expressed in noncancerous tissues, there exist limitations in their application to tumor immunotherapy. Livin/ML-IAP is one of recently identified inhibitor of apoptosis protein (IAP) family, which is overexpressed in melanoma cells. In this report, we show that Livin/ML-IAP is aberrantly expressed in many lung cancer cell lines and primary lung cancer tissues, whereas it is not detectable in normal tissues, including lung by reverse transcription-PCR methods. To identify HLA-A24-restricted T-cell epitopes of Livin/ML-IAP, eight peptides were selected from the amino acid sequence of this protein and screened for their binding affinity to HLA-A24. It was revealed that Livin7 peptide (amino acid sequence, KWFPSCQFLL) had the highest affinity to HLA-A24. By stimulating peripheral blood lymphocytes of HLA-A24-positive lung cancer patients with Livin7 peptide in vitro, the peptide-specific CTLs were successfully induced from four of five patients with Livin/ML-IAP-positive lung cancer but not from any of four patients without Livin/ML-IAP expression in their cancer tissues. Furthermore, the CTLs induced by Livin7 peptide showed cytotoxicity against Livin/ML-IAP(+) lung cancer cell lines in an HLA-A24-restricted manner. Our data suggest that Livin/ML-IAP may be an excellent target antigen in immunotherapy for lung cancer and Livin7 peptide may serve as a potent peptide vaccine for HLA-A*2402(+)/Livin(+) lung cancer patients.

Adaptor Proteins, Signal Transducing↗
PubMed2026

Predictive biomarkers in cancer immunotherapy for genitourinary malignancies.

Immunotherapy has transformed the management of genitourinary cancers, offering durable responses in selected patient groups. However, the clinical benefit of immune checkpoint inhibitors varies significantly across renal cell carcinoma, urothelial carcinoma, and prostate cancer, underscoring the need for reliable predictive biomarkers. This review summarizes current knowledge on established and emerging biomarkers, including PD L1 expression, tumor mutational burden, molecular subtypes, genomic alterations, tumor microenvironment characteristics, circulating biomarkers, microbiome influences, and multi omic integrative approaches. We discuss their potential clinical relevance, limitations, and applicability across different tumor types. Future directions emphasize the development of composite biomarkers, standardization of testing platforms, real time monitoring strategies, and the integration of advanced technologies such as artificial intelligence and spatial profiling. Understanding and validating these biomarkers will be essential for optimizing personalized immunotherapy in genitourinary cancers.

Circulating tumor DNA↗
PubMed2006

Cancer immunotherapy targeting the telomerase reverse transcriptase.

The human telomerase reverse transcriptase (hTERT) is expressed in more than 85% of tumor cells but is usually not found in normal cells, which makes hTERT as an ideal tumor-associate antigen (TAA) to develop potential vaccine specifically destroying cancers without impairing normal tissues in human cancer immunotherapy. Here are reviewed the fundamental advances of studies on immunogenicity of hTERT or its peptides and the early clinical trials using the hTERT vaccine approach in the last decades.

Antigens, Neoplasm↗
PubMed2002

Cancer immunotherapy with interleukin-2-activated natural killer cells.

Natural killer (NK) cells are a subset of lymphocytes with a distinct morphologic appearance (large granular lymphocytes [LGL]) and the ability to kill virally infected and tumor targets but to spare most normal cells. NK cells respond to a variety of biologic agents, such as interleukin-2 (IL-2), or interferons, by upregulation of cytolytic, secretory, and proliferative functions. In cancer-bearing hosts, NK cells have been considered to be the major component of antitumor immunity responsible for rapid elimination of malignant cells from the blood. More recently, however, studies have demonstrated the ability of adoptively transferred, IL-2-activated NK cells to selectively localize into solid tumors tissue and to eliminate established tumors. While these findings indicate a role for NK cells in cancer immunotherapy, additional studies are needed in both animal models and in humans to optimize clinical protocols of cancer therapy based on these cells.

Adoptive Transfer↗
PubMed2000

Heat shock proteins and cancer immunotherapy.

Vaccination with heat shock proteins from tumor have been shown to elicit an anti-tumor response. Current studies indicate that the immunogenicity of HSPs is derived from the antigenic peptides which they associate with. Mechanisms by which the HSP-peptide complexes induce an immune response and the possible role of HSPs in antigen presentation is discussed in this article. The use of HSP-peptide complexes can be used as tumor vaccines for cancer immunotherapy is reviewed.

Animals↗
PubMed1998

Immunocytokines: a promising approach to cancer immunotherapy.

Recombinant antibody-cytokine fusion proteins are immunocytokines that achieve high cytokine concentrations in the tumor microenvironment and thereby effectively stimulate cellular immune responses against malignancies. The activation and expansion of immune effector cells, such as CD8+ T lymphocytes, by interleukin-2 immunocytokines resulted in the eradication of established pulmonary and hepatic metastases of murine melanoma and colorectal carcinoma in syngeneic mouse models. These immunocytokines were equally effective in eliminating established bone marrow and liver metastases of murine neuroblastoma by activating natural killer cells. The effective eradication of metastases by immunocytokines resulted in significant prolongation in life span of mice over that of controls receiving equivalent mixtures of antibody and interleukin-2, which failed to reduce the growth of disseminated metastases. Proof of concept was established, indicating that immunocytokine-induced activation and expansion of immune effector cells in the tumor microenvironment can effectively eradicate established tumor metastases. This promising new approach to cancer immunotherapy may lead to clinical applications that improve treatment of cancer patients with minimal residual disease in an adjuvant setting.

Animals↗
PubMed2003

A novel approach to cancer immunotherapy: tumor cells decorated with CD80 generate effective antitumor immunity.

Malignant cells often elude the immune system by lacking costimulatory signals required for the generation of effective antitumor immunity. Immunization with tumor cells genetically modified to express costimulatory molecules is a highly promising approach to cancer immunotherapy. However, genetic modification of tumor cells is not only labor/time intensive but is also less efficient and bears safety concerns. To override these complications, we have recently developed a novel technology that allows for efficient and durable display of exogenous proteins on the surface of a cell within 2 h. This technology involves modification of the cell membrane with a biotin derivative and decoration of biotinylated cells with proteins chimeric with core streptavidin. A chimeric molecule composed of the extracellular domains of the human CD80 costimulatory molecule and core streptavidin (CD80-SA) was efficiently displayed on the cell surface, where it persisted with a t(1/2) of >10 days in vivo. Tumors from patients with advanced stage gynecologic cancers decorated with CD80-SA elicited potent ex vivo tumor-specific proliferative and cytotoxic responses in autologous lymphocytes. Immunization with tumor cells decorated with CD80-SA completely prevented tumor growth in an aggressive model of mouse lymphoma. This technology may serve as a fast, efficient, and safe alternative to gene transfer approaches for engineering tumor cells for use in immunotherapy and research.

Animals↗
PubMed2025

Oncogenic roles of young human de novo genes and their potential as neoantigens in cancer immunotherapy.

Young human de novo genes, recently emerging from non-coding regions, are expected to contribute to human-specific traits and diseases. However, systematic explorations of this connection have been lacking. Here, we report 37 recently originated de novo genes in humans, with their evolution and characteristics defined within an updated genomic context. The expression of these genes is significantly upregulated and temporospatially expanded in tumors, partially associated with extrachromosomal DNA amplification. Depletion of 57.1% of these genes suppresses tumor cell proliferation, underscoring their roles in tumorigenesis. As a proof of concept, we developed mRNA vaccines expressing ELFN1-AS1 and TYMSOS-young genes specifically expressed during early development but reactivated exclusively in tumors. In humanized mice, these vaccines triggered specific T cell activation and inhibited tumor growth. The antigens derived from these genes are immunogenic and capable of eliciting antigen-specific T cell activation in colorectal cancer patients. These findings underscore young human de novo genes as neoantigens in cancer immunotherapy.

Humans↗
PubMed2006

Molecular chaperones and cancer immunotherapy.

As one of the most abundant and evolutionally conserved intracellular proteins, heat shock proteins, also known as stress proteins or molecular chaperones, perform critical functions in maintaining cell homeostasis under physiological as well as stress conditions. Certain chaperones in extracellular milieu are also capable of modulating innate and adaptive immunity due to their ability to chaperone polypeptides and to interact with the host's immune system, particularly professional antigen-presenting cells. The immunomodulating properties of chaperones have been exploited for cancer immunotherapy. Clinical trials using chaperone-based vaccines to treat various malignancies are ongoing.

Animals↗
PubMed2003

Preparation of peptide-loaded dendritic cells for cancer immunotherapy.

Dendritic cell-based vaccines are being evaluated in clinical trials to determine their ability to activate clinically relevant tumor antigen-specific immune responses. Although some groups isolate dendritic cells from peripheral blood, most have found it more efficient to generate large numbers from peripheral blood progenitors, particularly plastic adherent or CD14+ monocytes, in media supplemented with GM-CSF and IL-4. These DC may then be matured, if desired, and loaded with antigen, such as tumor-associated peptides, prior to administration. We describe the scheme that we are currently using to generate peptide-loaded dendritic cells for our clinical trials of cancer immunotherapy.

CD40 Ligand↗
PubMed2004

Candidate epitope identification using peptide property models: application to cancer immunotherapy.

Peptides derived from pathogens or tumors are selectively presented by the major histocompatibility complex proteins (MHC) to the T lymphocytes. Antigenic peptide-MHC complexes on the cell surface are specifically recognized by T cells and, in conjunction with co-factor interactions, can activate the T cells to initiate the necessary immune response against the target cells. Peptides that are capable of binding to multiple MHC molecules are potential T cell epitopes for diverse human populations that may be useful in vaccine design. Bioinformatical approaches to predict MHC binding peptides can facilitate the resource-consuming effort of T cell epitope identification. We describe a new method for predicting MHC binding based on peptide property models constructed using biophysical parameters of the constituent amino acids and a training set of known binders. The models can be applied to development of anti-tumor vaccines by scanning proteins over-expressed in cancer cells for peptides that bind to a variety of MHC molecules. The complete algorithm is described and illustrated in the context of identifying candidate T cell epitopes for melanomas and breast cancers. We analyzed MART-1, S-100, MBP, and CD63 for melanoma and p53, MUC1, cyclin B1, HER-2/neu, and CEA for breast cancer. In general, proteins over-expressed in cancer cells may be identified using DNA microarray expression profiling. Comparisons of model predictions with available experimental data were assessed. The candidate epitopes identified by such a computational approach must be evaluated experimentally but the approach can provide an efficient and focused strategy for anti-cancer immunotherapy development.

Animals↗
PubMed2004

DCs and CD40-activated B cells: current and future avenues to cellular cancer immunotherapy.

Despite the still poorly understood complexity of tumor-host immune interactions, the use of cellular vaccines (particularly dendritic cells) has made it possible to reliably generate tumor antigen-specific T cells, both in animal models and in humans. These encouraging pre-clinical results have led to a translation of these immunotherapeutic strategies into clinical trials. With numerous trials still underway, their general outcome has so far been disappointing, and the discrepancy between pre-clinical data and clinical response rates is striking. Thus, either the pre-clinical models have not been representative of the human situation or the translation into human clinical trials is still sub-optimal. Here we suggest new avenues of clinical research to further improve cellular cancer immunotherapy.

Animals↗
PubMed2005

Cancer immunotherapy based on killing of Salmonella-infected tumor cells.

A major obstacle for the development of effective immunotherapy is the ability of tumors to escape the immune system. The possibility to kill tumor cells because they are recognized as infected rather than as malignant could help overcome immune escape mechanisms. Here we report a conceptually new approach of cancer immunotherapy based on in vivo infection of tumors and killing of infected tumor cells. Attenuated but still invasive, Salmonella typhimurium can be successfully exploited to invade melanoma cells that can present antigenic determinants of bacterial origin and become targets for anti-Salmonella-specific T cells. However, to fully appreciate the anticancer therapeutic properties of S. typhimurium, tumor-bearing mice need to be vaccinated against S. typhimurium before intratumoral Salmonella injection. Tumor infection when coupled to anti-Salmonella vaccination leads to 50% to 100% tumor-free mice with a better outcome on larger tumors. Invasive Salmonella also exert an indirect toxic effect on tumor cells through the recruitment of inflammatory cells and the cross-presentation of tumor antigens, which allow induction of tumor-specific immune response. This is effective in retarding the growth of untreated established distant tumors and in protecting the mice from subsequent tumor challenges.

Animals↗
PubMed2000

Adjuvant histamine in cancer immunotherapy.

Interleukin-2 (IL-2) is an effective activator of lymphocytes with anti-neoplastic properties such as T-cells or natural killer cells, and this property of IL-2 has formed the basis for its widespread used as an immunotherapeutic agent in human neoplastic disease. In recent years, IL-2 therapy for solid neoplastic diseases and hematopoietic cancers has been supplemented with histamine dihydrochloride with the aim of counteracting immunosuppressive signals from monocytes/macrophages. Here we review the preclinical basis for the use of histamine as an adjunct to IL-2 in cancer immunotherapy.

Animals↗
PubMed2005

Cancer immunotherapy based on the killing of Salmonella typhimurium-infected tumour cells.

The use of bacteria for anticancer purposes was first attempted over 100 years ago. Recently, several strains of Salmonella have been shown to possess anticancer activity and, interestingly, Salmonella possesses a unique propensity to track to tumour tissue in vivo. This review presents the use of Salmonella for cancer immunotherapy, including the distinguishing characteristics of this organism and preclinical as well as clinical data.

Animals↗
PubMed1981

Optimized mitochondrial function as a nutritional strategy in cancer immunotherapy.

Activated macrophages require effective mitochondrial function, but mitochondrial efficiency is jeopardized by the free radicals produced naturally in macrophage metabolism. This perspective rationalizes the well-documented immunostimulant effects of coenzyme Q and of antioxidant nutrients such as selenium, vitamin E, and manganese. More generally, the nutritional optimization of mitochondrial function is proposed as a "neo-Warburgian' approach to cancer immunotherapy.

Antioxidants↗
PubMed2003

Gene expression profiling and functional activity of human dendritic cells induced with IFN-alpha-2b: implications for cancer immunotherapy.

PURPOSE: In this study, we have compared patterns of gene expression and functional activity of human dendritic cells (DCs) cultured under defined conditions in IFN-alpha-2b and recombinant human granulocyte macrophage colony-stimulating factor (DCA) with cells grown in granulocyte macrophage colony-stimulating factor and IL-4 (DC4) as an initial step in evaluating the clinical utility of DCA in cancer immunotherapy. EXPERIMENTAL DESIGN AND RESULTS: Comparison of mRNA transcript profiles between DCA and DC4 revealed different expression patterns for cytokines, chemokines, chemokine receptors, costimulatory molecules, and adhesion proteins. Many genes involved in antigen (Ag) processing were equally expressed in both populations; however, expression of transcripts involved in Ag presentation was increased in DCA. DCA also showed up-regulation of Toll-like receptor 2 and 3, as well as several tumor necrosis factor family ligands. Consistent with expression profiling, functional assays demonstrated that DCAs were more potent stimulators of naive T-cell responses than DC4 in an interleukin 15 and interleukin 1beta-dependent manner. DCA-mediated tumor cell-directed cytotoxicity induced apoptosis in different human tumor cell lines and internalized apoptotic bodies to a greater extent than DC4. Lastly, in vitro priming experiments, using apoptotic cells or peptide as sources of Ag, showed that DCA drove the expansion of tumor peptide Ag-specific autologous CD8+ T cells to a greater extent than DC4. CONCLUSIONS: The unique phenotype conferred by culturing DCs in IFN-alpha-2b may be useful in adoptive transfer regimens where the destruction of tumor cells in situ, initiation of T-cell responses toward tumor tissue with unknown Ags, and/or enhancement of pre-existing Ag-specific memory responses are desired outcomes.

Apoptosis↗