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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 The prevalence and predictors of using herbal medicines among Iranian cancer patients. Complement Ther Clin Pract. 2019 May;35:368-373 Authors: Bazrafshani MS, Khandani BK, Pardakhty A, Tajadini H, Pour Afshar RM, Moazed V, Nemati A, Nasiri N, Sharifi H Abstract BACKGROUND: and Purpose: Using of herbal medicines is common for cancer treatment. The aim of this study was to determine the prevalence, reasons, and predicting factors for the use of herbal medicines by Iranian cancer patients. MATERIALS AND METHODS: We conducted this cross-sectional study on 315 cancer patients through face-to-face interview in Kerman, Southeast of Iran, 2017. RESULTS: In total, 267 (84.1%) patients used at least one herbal medicine during chemotherapy courses, while only 42 (16.1%) patients discussed the use of herbal medicines with physicians. Living in urban regions (OR, 2.56; 95% CI, 1.30-5.05; P<0.0001) and the experience of constipation and diarrhea (OR, 2.11; 95% CI, 1.09-4.05; P = 0.02) were determined as some predicting factors for the use of herbal medicines. CONCLUSION: Our findings indicate that as herbal medicines are common among cancer patients and their use is often overlooked, physicians should pay particular attention to herbal medicines during chemotherapy. PMID: 31003684 [PubMed - in process]
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Related Articles Lower platelet count with increased density of platelet antigens in granulocyte colony-stimulating factor mobilized peripheral blood stem cell donors. J Formos Med Assoc. 2019 Apr 16;: Authors: Wu YF, Gu MH, Yang SH, Wang TF Abstract BACKGROUND/PURPOSE: Granulocyte colony-stimulating factor (G-CSF) is widely used for prophylaxis and treatment of neutropenia in cancer patients and also for peripheral blood stem cells (PBSC) mobilization. The aim of this study is to evaluate the possible changes of platelet surface antigens after G-CSF injection in PBSC donors compared with healthy control. METHODS: Between January 1st and December 31st, 2014, 48 healthy voluntary PBSC donors were eligible for this study. Donors received G-CSF (Filgrastim) subcutaneously for five days, and then their whole blood was collected for complete blood count. Analysis of platelet antigens was performed by flow cytometry. Sixteen healthy controls were also included for comparison. RESULTS: Lower platelet counts were found in PBSC donors after G-CSF use and in comparison with health controls. The platelet size evaluated by forward scattering (FSC) showed smaller platelets in PBSC donors after G-CSF use compared with healthy controls (39.3 vs 46.7 mean fluorescence intensity, P = 0.015). CD31 were higher in PBSC donor (203.2 vs. 120.7, P < 0.001). Except CD31, other platelet surface antigens were not different between PBSC donors and healthy controls. After adjusting by FSC data, the mean antigen intensity/FSC of CD31, CD41a, CD42a, CD42b and CD61 showed 5.45 vs 2.78 (P < 0.001), 4.35 vs 3.47 (P = 0.007), 3.87 vs 3.17 (P = 0.015), 20.45 vs 16.94 (P = 0.045), and 5.98 vs 4.88 (P = 0.018) respectively. CONCLUSION: We noted higher density of platelet surface antigens, lower platelet count and smaller platelet size after G-CSF injection. PMID: 31003920 [PubMed - as supplied by publisher]
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Related Articles Allogeneic hematopoietic cell transplantation improves outcome of adults with t(6;9) acute myeloid leukemia - results from an international collaborative study. Haematologica. 2019 Apr 19;: Authors: Kayser S, Hills RK, Luskin MR, Brunner AM, Terré C, Westermann J, Menghrajani K, Shaw C, Baer MR, Elliott MA, Perl AE, Ráčil Z, Mayer J, Zak P, Szotkowski T, de Botton S, Grimwade D, Mayer K, Walter RB, Krämer A, Burnett AK, Ho AD, Platzbecker U, Thiede C, Ehninger G, Stone RM, Röllig C, Tallman MS, Estey EH, Müller-Tidow C, Russell NH, Schlenk RF, Levis MJ Abstract Acute myeloid leukemia with t(6;9)(p22;q34) is a distinct entity accounting for 1-2% of acute myeloid leukemia cases. A substantial proportion of these patients have a concomitant FLT3-ITD. While outcomes are dismal with intensive chemotherapy, limited evidence suggests allogeneic hematopoietic cell transplantation may improve survival if applied early during first complete remission. We report on a cohort of 178 patients with t(6;9)(p22;q34) within an international, multicenter collaboration. Median age was 46 (range: 16-76) years, acute myeloid leukemia was de novo in 88%, FLT3-ITD was present in 62%, and additional cytogenetic abnormalities in 21%. Complete remission was achieved in 81% (n=144), including 14 patients who received high-dose cytarabine after initial induction failure. With a median follow-up of 5.43 years, estimated overall survival at 5 years was 38% (95%-CI, 31-47%). Allogeneic hematopoietic cell transplantation was performed in 117 (66%) patients, including 89 in first complete remission. Allogeneic hematopoietic cell transplantation in first complete remission was associated with higher 5-year relapse-free and overall survival as compared to consolidation chemotherapy (45% [95%-CI, 35-59%] and 53% [95%-CI, 42-66%], vs. 7% [95%-CI, 3-19%] and 23% [95%-CI, 13-38%]. For patients undergoing allogeneic hematopoietic cell transplantation, overall survival rates at 5 years did not differ whether performed in first (53% [95%-CI, 42-66%]), or second complete remission (58% [95%-CI, 31-100%]; n=10) or with active disease/relapse (54% [95%-CI, 34-84%]; n=18) (P=0.67). Neither FLT3-ITD nor additional chromosomal abnormalities impacted survival. In conclusion, outcomes of t(6;9)(p22;q34) acute myeloid leukemias are poor with chemotherapy, and can be substantially improved with allogeneic hematopoietic cell transplantation. PMID: 31004014 [PubMed - as supplied by publisher]
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