Cancer Stem Cell Treatment

Autologous Dendritic Cell Therapy for Cancer is available at SIRM

Cancer represents one of the major causes of mortality worldwide. More than half of patients suffering from cancer succumb to their condition. The primary approaches to treating cancer are surgical resection followed by radiation therapy and chemotherapy. These treatments have resulted in significant benefits to patients with the majority of tumor types, and the clinical outcomes have become more satisfactory. It is recognized that multidisciplinary treatments should be used in cancer treatments, another option proposed for this is immunotherapy. The combination of the traditional methods of surgery, chemotherapy and radiotherapy with immunotherapy, is a new way for anti-cancer therapies to reduce the mortality of cancer patients. The dysfunction of the antigen-specific T cells required to kill the cancer leads to cancer cells being able to grow in cancer patients. Active and adoptive T cell immunotherapies generate T cells that can target cancer cells.

Dendritic cells (DCs) are immune cells that function as antigen-presenting cells. They are able to activate naive CD4+ T helper cells and unprimed CD8+ cytotoxic T lymphocytes. Active immunotherapy, represented by DC-based regimens, has been used to produce tumor-specific antigen-presenting cells and to generate cytotoxic T lymphocyte responses against cancer cells. DCs can capture antigens, process them, and present them with co-stimulation cytokines/messengers to initiate an immune response, like inducing primary T-cell responses.

Adoptive immunotherapy, as conducted at our Asian Stem Cell Institute, is a personalized therapy that uses a patient’s own anti-tumor immune cells to kill cancer cells and may be used to treat several types of cancer, and represents another therapeutic approach against cancer. To date, the adoptive immunotherapy approach is one of the most effective methods for using the body’s immune system to treat cancer. To be used clinically, protocols for the development of these functional DCs must be established for in-clinic use via defined, xenobiotic-free medium conditions.

The purpose of the present study is to determine the cellular immune response in terms of the delayed-type hyper-sensitivity (DTH) skin test and evaluate the subjective clinical outcome and safety of the regimen in cancer patients receiving a DC vaccine.

Vaccination against a single antigen is available using purified and synthetic products, but these have disadvantages because it is unknown which of the identified antigens have the potential to induce an effective antitumor immune response. This study uses unfractionated, autologous, tumor-derived antigens in the form oftumor cell lysates which circumvents this disadvantage.

Tumor lysates as addressed in this protocol, contain multiple known as well as unknown antigens that can be presented to T cells by both MHC class I- and class II-pathways. Therefore, lysate-loaded DCs are more likely to induce the more preferred polyclonal expansion of T cells, including MHC class II restricted T-helper cells. These have been recognized to play an important role in the activation of Cytotoxic T Lymphocytes (CTLs), probably the most important cells in effecting an antitumor immune response. The generation of CTL clones with multiple specificities may be an advantage in heterogeneous tumors and could also reduce the risk of tumor escape variants. Furthermore, lysate from the autologous tumor can be used independently of the HLA type of the patient. A drawback of unfractionated tumor antigens is the possibility of inducing an autoimmune reactivity to epitopes that are shared by normal tissues. However, in clinical trials using lysate or whole tumor cells as the source of antigen, no clinically relevant autoimmune responses have ever been detected.

Personalized dendritic cell vaccines for cancer, via adoptive immunotherapy, are successfully developed and autologously administered to patients coming to Asia, and more specifically, within the Philippines at the Subic Institute for Regenerative Medicine. The results of this case study of cancer and immunotherapy via pulsed dendritic cells, can serve as another example of safety for future cancer vaccine development.

Dendritic Cell Therapy for Cancer:
Related Articles A generic RNA pulsed DC based approach for developing therapeutic intervention against nasopharyngeal carcinoma. Hum Vaccin Immunother. 2017 Apr 03;13(4):854-866 Authors: Tyagi RK, Parmar R, Patel N Abstract The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs). The RNA extracted from well-characterized highly immunogenic NPC cells (C666-1) was transfected into MoDCs. The formulated and characterized cationic liposomes were used to achieving efficient RNA transfection of immature DCs. Further, DCs were forcibly matured with a cytokine cocktail to achieve greater expression of MHC and co-stimulatory molecules. Moreover, our results did not see any effect of RNA or lipids on MoDCs phenotype or cytokine expression. RNA loaded DCs derived from HLA-A2-positive donors were shown to activate effector memory cytotoxic T lymphocytes (CTLs) specific for TAAg ligand expressed by C666-1 cells. Our results show the comparison of cytotoxic response mounted against RNA-loaded DCs with those directly stimulated by C666-1 tumor cells. Our findings suggest that DCs expressing tumor cell RNA primed naïve T cells show T cells priming with lesser cytotoxicity and cytokine secretion when exposed with with C666-1 tumor cells. These results surface the potential of DCs to deliver RNA in NPCs, sufficient presentation of RNA to provoke perdurable immune responses against nasopharyngeal carcinoma. Our results implies that DC based vaccine approach may be useful to develop therapeutic interventional approach in the form of vaccine to address NPCs. PMID: 27901642 [PubMed - indexed for MEDLINE]
Related Articles Inflammatory Manifestations of Lymphedema. Int J Mol Sci. 2017 Jan 17;18(1): Authors: Ly CL, Kataru RP, Mehrara BJ Abstract Lymphedema results from lymphatic insufficiency leading to a progressive inflammatory process that ultimately manifests as discomfort, recurrent infections, and, at times, secondary malignancy. Collectively, these morbidities contribute to an overall poor quality of life. Although there have been recent advances in microsurgical interventions, a conservative palliative approach remains the mainstay of treatment for this disabling disease. The absence of a cure is due to an incomplete understanding of the pathophysiological changes that result in lymphedema. A histological hallmark of lymphedema is inflammatory cell infiltration and recent studies with animal models and clinical biopsy specimens have suggested that this response plays a key role in the pathology of the disease. The purpose of this report is to provide an overview of the ongoing research in and the current understanding of the inflammatory manifestations of lymphedema. PMID: 28106728 [PubMed - indexed for MEDLINE]
Related Articles Nanotechnology based therapeutic modality to boost anti-tumor immunity and collapse tumor defense. J Control Release. 2017 Apr 20;: Authors: Hu X, Wu T, Bao Y, Zhang Z Abstract Cancer is still the leading cause of death. While traditional treatments such as surgery, chemotherapy and radiotherapy play dominating roles, recent breakthroughs in cancer immunotherapy indicate that the influence of immune system on cancer development is virtually beyond our expectation. Manipulating the immune system to fight against cancer has been thriving in recent years. Further understanding of tumor anatomy provides opportunities to put a brake on immunosuppression by overcoming tumor intrinsic resistance or modulating tumor microenvironment. Nanotechnology which provides versatile engineered approaches to enhance therapeutic effects may potentially contribute to the development of future cancer treatment modality. In this review, we will focus on the application of nanotechnology both in boosting anti-tumor immunity and collapsing tumor defense. PMID: 28434891 [PubMed - as supplied by publisher]
Related Articles Adenocarcinoma of the appendix occurring in a patient treated with paclitaxel for locally advanced esophageal cancer. J Oncol Pharm Pract. 2017 Jan 01;:1078155217689947 Authors: Dasanu CA, Hyams DM, Senatore FJ Abstract Paclitaxel has been linked with a number of immunosuppressive effects such as decreased numbers and activity of dendritic cells, NK-cells and monocytes, which may in turn lead to defective T-cell activation. In addition, this agent was shown to cause mitotic arrest resembling high-grade dysplasia throughout the gastrointestinal tract, including the appendix. We have previously documented a series of lung cancer patients who developed pre-malignant colonic polyps and/or colon cancer either during or weeks following chemotherapy with paclitaxel, suggesting a potential role of this agent in their pathogenesis. We describe herein a patient who developed adenocarcinoma of the appendix five months after paclitaxel therapy for a locally advanced lower esophageal cancer. Although the cancer of the appendix was in early stage, it was poorly differentiated and showed lymphovascular invasion. The context, timeline and existing experience suggest that this second cancer was triggered by a pre-existing insult, conceivably delivered by paclitaxel. PMID: 28436298 [PubMed - as supplied by publisher]

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