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1

Considerations on clinical use of T Cell immunotherapy for cancer

100%
Plautz G. E., Cohen P. A., Shu S.
Archivum Immunologiae et Therapiae Experimentalis
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2003
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vol. 51
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issue 4
245-257
EN
The recognition by effector T lymphocytes of novel antigenic targets on tumor cells is the premise of specific targeted immunotherapy of cancer. With the molecular characterization of peptide epitopes from melanoma antigens, and more recently broadly expressed tumor antigens, there has been considerable enthusiasm for clinical evaluation of peptide tumor vaccines. Immunologic monitoring of vaccinated patients has demonstrated expansion of CD8+ T cells that react with the relevant peptide and, more importantly, with native tumor. In most instances however, vaccine-induced CD8+ T cell responses alone have not been sufficiently robust or sustained to translate into a high percentage of durable clinical responses. Vaccine strategies have also utilized dendritic cells (DCs) that have been modified to present tumor antigens. The superior antigen processing capacity and co-stimulatory function of DC convey a powerful stimulatory signal to both CD4+ and CD8+ T cells. Several strategies are attempting to broaden the immune response beyond single antigens by introducing the entire complement of tumor antigens into DCs. Adoptive immunotherapy is a promising strategy to recover tumor-reactive precursor T cells from patients, stimulate them to induce numerical expansion, and then re-infuse them. Ex vivo manipulation of the tumor-reactive T cells also permits cytotoxic therapy to be administered to the patient without damaging the effector cells. Recently, host lymphodepletion prior to adoptive transfer of effector T cells has resulted in an extremely high and sustained frequency of effectors that has achieved therapeutic efficacy against bulky metastatic disease in a substantial fraction of treated patients.
2

Molecular addresses of tumors: selection by in vivo phage display

100%
Li X.-B., Schluesener H. J., Xu S. Q.
Archivum Immunologiae et Therapiae Experimentalis
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2006
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vol. 54
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issue 3
177-181
EN
In vivo phage display has been used extensively to screen for novel targets of tumor therapy. Phage display peptide libraries can express random peptides or protein fragments and the aim of phage display is to identify peptide molecules that bind stably to a given target. Angiogenesis is essential to tumor development. Both blood and lymphatic vessels of tumors are different from those of normal tissues. Phage display has been used to analyze the structure and molecular diversity of tumor vasculature and to select tumor-specific antigens which have revealed stage- and type-specific markers of tumor blood vessels. Furthermore, peptides identified by in vivo phage display also work as vehicles to transport cargo therapeutic reagents to tumors. These peptides and their corresponding cellular proteins and ligands may provide molecular tools to selectively target the addresses of tumors and their pathological blood vessels and might increase the efficacy of therapy while decreasing side effects.
3

Dendritic cells and their application in cancer immunotherapy - achievements and future prospects

88%
Rossowska J., Pajtasz-Piasecka E.
Postępy Higieny i Medycyny Doświadczalnej
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2003
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vol. 57
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issue 5
501-518
EN
Dendritic cells (DC) are generally believed to play a key role in the initiation of immune response. A potential usefulness of these cells in antitumor immunotherapy is strongly considered in every stage of cancer treatment. Studies on tumor tissue infiltration by immune cells shown, that DC represented only a small percentage of leukocytes. The influence of tumor environment resulted in reduction of DC number, their inability to migrate across endothelial barriers, or impaired maturation and efficiency of tumor antigens presentation. Thus, decreased number of DC in tumors could be associated with a bad prognosis. Many attempts concentrate on the creation of the DC-based vaccines, which would generate strong anticancer cell mediated immunity. They include studies on stage of differentiation of the administered DC; effective way for antigen loading; optimum route and schedule of DC delivery into tumor bearing host; effective vectors for the therapeutic genes; effects of the therapy based on cytokine secreting DC; influence of DC on co-operation between innate and acquired immunity as well as on the generation of specific antitumor response. This review is focused on two important areas aiming for the preparation of DC vaccine for effective stimulation of immune response: - loading of DC with tumor antigens (or other ways of DC preparation to successful antigen presentation) - as an encouraging evidence of therapeutic efficacy, and - genetic modification of DC with cytokines resulting in the stimulation or alteration of the antitumor DC activity - as a promising anticancer strategy.
4

Immune reaction to breast cancer: for better or for worse?

88%
Ogmundsdotti H. M.
Archivum Immunologiae et Therapiae Experimentalis
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2001
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vol. 49
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issue 2 suppl.
75-82
EN
The infiltration of breast carcinomas with lymphoid cells has often been interpreted as an indication of an active immune response against the tumor and thus a favorable prognostic sign. Several studies have, however, cast doubt on this assumption. In situ breast carcinomas are more common than invasive cancers and it may be speculated that immune surveillance plays a role in preventing some localized cancers from becoming invasive. A secondary type of immune surveillance might be implicated in the long persistence of dormant breast carcinoma cells in the bone marrow. Breast cancer cells can carry tumor-associated antigens, particularly MUC1. These may elicit specific antibody responses but there is less evidence for a CTL response. There are indications that professional antigen presenting cells may be present and active at the edge breast tumours. Breast cancer cells may also interact directly with macrophages and NK cells. In terms of immune effector mechanisms in breast cancer, the communication with potential effector cells is likely to be often faulty because of altered expression of HLA class I molecules. Pleiotrophic cytokines are frequently present and could have a variety of effects ranging from growth inhibition to stimulated proliferation, loss of cell adhesion and activation of matrix degrading enzymes. Fas ligand is unlikely to play a role in the immune evasion of breast cancer. There is thus evidence for a variety of immune reactions to breast cancer. It is possible that they mediate some form surveillance, but growing, invasive tumors have escape routes and may even use cytokines to their advantage.
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