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  1. Immunotherapy and Targeted Therapy in the Management of Oral Cancers
    Dutta S, Singhal S, Shah RB, Haque M
    Crit Rev Oncog, 2022;27(4):23-37.
    PMID: 37199300 DOI: 10.1615/CritRevOncog.2022046361
    Oral cancers (OCs), being one of the frequent malignancies in the head and neck region, need prompt diagnosis and treatment. Apart from basic therapeutic modalities, immunotherapy has now been utilized as a novel approach to combat the disease. With the comprehension of the strategies adopted by cancer cells to evade the immune elimination by the body's immune system, targeted immunotherapies have now become the core area of research. The immune expression of epidermal growth factor receptor (EGFR), programmed cell death protein ligand-1 (PDL-1), etc., are enhanced in OC and have been associated with evasion of the immune system. Targeted immunotherapies now include monoclonal antibodies targeting EGFR like cetuximab and panitumumab, programmed cell death-1 (PD-1) inhibitors like pembrolizumab, cemiplimab, and nivolumab, and PD-L1 inhibitors like atezolizumab, avelumab, and durvalumab. Targeted immunotherapies like chimeric antigen receptor T-cell treatment and small molecule inhibitors are in several clinical trials tried as monotherapy and adjuvant immunotherapy and have shown promising results. Other immunothera-peutic approaches such as cytokines like interferons or interleukins, vaccines, and gene therapy have also been an area of research for the management of OC. However, the cautious selection of appropriate patients with specific immune characteristics as a candidate for immunotherapeutic agents is a crucial component of targeted immunotherapy. This article elaborates on the immune contexture of oral cancer cells, the mechanism of immune evasion by cancer cells, targets for immunotherapies, existent immunotherapeutic agents, and prospects in the field of immunotherapy.
    Matched MeSH terms: Immunotherapy/methods
  2. Fulltext Dendritic cell immunobiology and potential roles in immunotherapy
    Fadilah SA, Cheong SK
    Malays J Pathol, 2007 Jun;29(1):1-18.
    PMID: 19108040 MyJurnal
    Owing to the importance of dendritic cells (DC) in the induction and control of immunity, an understanding of their biology is central to the development of potent immunotherapies for cancer, chronic infections, autoimmune disease, and induction of transplantation tolerance. This review surveys the heterogeneity of DC with regards to their phenotype and developmental origin, and how they initiate, modify and regulate the immune response, with emphasis on their maturation, migration, antigen-presentation and interaction with T cells and other immune cells. Much of this knowledge is obtained through research on murine DC. Research on human DC has been hampered by limitations associated with in vitro assays and limited access to human tissues. New approaches on human DC research are required in order to develop novel strategies for the treatment of microbial infections, the control of graft rejection, and the improvement of DC-based immunotherapeutic protocols for autoimmunity, allergy, and cancer.
    Matched MeSH terms: Immunotherapy/methods*
  3. Recent advances in tau-directed immunotherapy against Alzheimer's disease: an overview of pre-clinical and clinical development
    Ng PY, Chang IS, Koh RY, Chye SM
    Metab Brain Dis, 2020 10;35(7):1049-1066.
    PMID: 32632666 DOI: 10.1007/s11011-020-00591-6
    Alzheimer's disease (AD) has been a worldwide concern for many years now. This is due to the fact that AD is an irreversible and progressive neurodegenerative disease that affects quality of life. Failure of some Phase II/III clinical trials in AD targeting accumulation of β-amyloid in the brain has led to an increase in interest in studying alternative treatments against tubulin-associated unit (Tau) pathology. These alternative treatments include active and passive immunisation. Based on numerous studies, Tau is reported as a potential immunotherapeutic target for tauopathy-related diseases including AD. Accumulation and aggregation of hyperphosphorylated Tau as neuropil threads and neurofibrillary tangles (NFT) are pathological hallmarks of AD. Both active and passive immunisation targeting Tau protein have shown the capabilities to decrease or prevent Tau pathology and improve either motor or cognitive impairment in various animal models. In this review, we summarise recent advances in active and passive immunisation targeting pathological Tau protein, and will discuss with data obtained from both animal and human trials. Together, we give a brief overview about problems being encountered in these immunotherapies.
    Matched MeSH terms: Immunotherapy/methods*
  4. Case Report: Cord blood-derived natural killer cells as new potential immunotherapy drug for solid tumor: a case study for endometrial cancer
    Mu Y, Tong J, Wang Y, Yang Y, Wu X
    Front Immunol, 2023;14:1213161.
    PMID: 37457710 DOI: 10.3389/fimmu.2023.1213161
    Adoptive transfer of natural killer (NK) cells represents a viable treatment method for patients with advanced malignancies. Our team previously developed a simple, safe, and cost-effective method for obtaining high yields of pure and functional NK cells from cord blood (CB) without the need for cell sorting, feeder cells, or multiple cytokines. We present the case of a 52-year-old female patient diagnosed with poorly differentiated stage IVB (T3N2M1) endometrial cancer, who exhibited leukemoid reaction and pretreatment thrombocytosis as paraneoplastic syndromes. The patient received two courses of CB-derived NK (CB-NK) cell immunotherapy between March and September 2022, due to her extremely low NK cell activity. Two available CB units matched at 8/10 HLA with KIR-mismatch were chosen, and we were able to produce NK cells with high yield (>1.0×1010 NK cells), purity (>90%), and function (>80%) from CB without cell sorting, feeder cells, or multiple cytokines. These cells were then adoptively transferred to the patient. No adverse effects or graft-versus-host disease were observed after infusion of CB-NK cells. Our clinical experience supports the efficacy of CB-NK cell treatment in increasing NK cell activity, depleting tumor activity, improving quality of life, and reducing the size of abdominal and pelvic masses with the disappearance of multiple lymph node metastases through the regulation of systemic antitumor immunity. Remarkably, the white blood cell and platelet counts decreased to normal levels after CB-NK cell immunotherapy. This clinical work suggests that CB-NK cell immunotherapy holds promise as a therapeutic approach for endometrial cancer.
    Matched MeSH terms: Immunotherapy/methods
  5. Fulltext Recent advances in Toxoplasma gondii immunotherapeutics
    Lim SS, Othman RY
    Korean J Parasitol, 2014 Dec;52(6):581-93.
    PMID: 25548409 DOI: 10.3347/kjp.2014.52.6.581
    Toxoplasmosis is an opportunistic infection caused by the protozoan parasite Toxoplasma gondii. T. gondii is widespread globally and causes severe diseases in individuals with impaired immune defences as well as congenitally infected infants. The high prevalence rate in some parts of the world such as South America and Africa, coupled with the current drug treatments that trigger hypersensitivity reactions, makes the development of immunotherapeutics intervention a highly important research priority. Immunotherapeutics strategies could either be a vaccine which would confer a pre-emptive immunity to infection, or passive immunization in cases of disease recrudescence or recurrent clinical diseases. As the severity of clinical manifestations is often greater in developing nations, the development of well-tolerated and safe immunotherapeutics becomes not only a scientific pursuit, but a humanitarian enterprise. In the last few years, much progress has been made in vaccine research with new antigens, novel adjuvants, and innovative vaccine delivery such as nanoparticles and antigen encapsulations. A literature search over the past 5 years showed that most experimental studies were focused on DNA vaccination at 52%, followed by protein vaccination which formed 36% of the studies, live attenuated vaccinations at 9%, and heterologous vaccination at 3%; while there were few on passive immunization. Recent progress in studies on vaccination, passive immunization, as well as insights gained from these immunotherapeutics is highlighted in this review.
    Matched MeSH terms: Immunotherapy/methods*
  6. Fulltext Towards an HIV cure: science and debate from the International AIDS Society 2013 symposium
    Purcell DF, Elliott JH, Ross AL, Frater J
    Retrovirology, 2013 Nov 13;10:134.
    PMID: 24224983 DOI: 10.1186/1742-4690-10-134
    The International AIDS Society convened the multi-stakeholder "Towards an HIV Cure" symposium in Kuala Lumpur, Malaysia in 2013 to address the significant research challenges posed by the search for a cure for HIV infection. Current antiretroviral regimens select for a small reservoir of cells that harbour latent HIV provirus, produce few or no HIV virions, and resist detection or clearance by host immunity. The symposium examined basic molecular science and animal model data, and emerging and ongoing clinical trial results to prioritise strategies and determine the viral and immune responses that could lead to HIV remission without ART. Here we review the presentations that scrutinized the molecular mechanisms controlling virus expression from proviral DNA, and the intrinsic cellular restriction and immune mechanisms preventing viral production. Insights from the basic science have translated into new therapeutic strategies seeking HIV remission without ongoing therapy, and much interest was focused on these ongoing trials. We also summarise the emerging ethical issues and patient expectations as concepts move into the clinic.
    Matched MeSH terms: Immunotherapy/methods*
  7. Fulltext Recent advances targeting innate immunity-mediated therapies against HIV-1 infection
    Shankar EM, Velu V, Vignesh R, Vijayaraghavalu S, Rukumani DV, Sabet NS
    Microbiol. Immunol., 2012 Aug;56(8):497-505.
    PMID: 22900503 DOI: 10.1111/j.1348-0421.2012.00485.x
    Early defence mechanisms of innate immunity respond rapidly to infection against HIV-1 in the genital mucosa. Additionally, innate immunity optimises effective adaptive immune responses against persistent HIV infection. Recent research has highlighted the intrinsic roles of apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G, tripartite motif-containing protein 5, tetherin, sterile α-motif and histidine/aspartic acid domain-containing protein 1 in restricting HIV-1 replication. Likewise, certain endogenously secreted antimicrobial peptides, namely α/β/θ-defensins, lactoferrins, secretory leukocyte protease inhibitor, trappin-2/elafin and macrophage inflammatory protein-3α are reportedly protective. Whilst certain factors directly inhibit HIV, others can be permissive. Interferon-λ3 exerts an anti-HIV function by activating Janus kinase-signal transducer and activator of transcription-mediated innate responses. Morphine has been found to impair intracellular innate immunity, contributing to HIV establishment in macrophages. Interestingly, protegrin-1 could be used therapeutically to inhibit early HIV-1 establishment. Moreover, chloroquine inhibits plasmacytoid dendritic cell activation and improves effective T-cell responses. This minireview summarizes the recently identified targets for innate immunity-mediated therapies and outlines the challenges that lie ahead in improving treatment of HIV infection.
    Matched MeSH terms: Immunotherapy/methods*
  8. The role of immunotherapy in Guillain-Barré syndrome: understanding the mechanism of action
    Shahrizaila N, Yuki N
    Expert Opin Pharmacother, 2011 Jul;12(10):1551-60.
    PMID: 21473704 DOI: 10.1517/14656566.2011.564160
    Guillain-Barré syndrome (GBS) is the most frequent cause of acute flaccid paralysis and, despite treatment, there continues to be an associated mortality and severe disability ranging from 9 to 17%. This article reviews the rationale behind the existing immunotherapy in GBS and discusses the future direction that work in this area should follow.
    Matched MeSH terms: Immunotherapy/methods
  9. Sublingual immunotherapy in patients with house dust mite allergic rhinitis: prospective study of clinical outcomes over a two-year period
    Soh JY, Thalayasingam M, Ong S, Loo EX, Shek LP, Chao SS
    J Laryngol Otol, 2016 Mar;130(3):272-7.
    PMID: 26781592 DOI: 10.1017/S0022215116000025
    BACKGROUND: Sublingual immunotherapy in patients with allergic rhinitis sensitised to house dust mites is safe, but its efficacy is controversial and sublingual immunotherapy with Blomia tropicalis has not yet been studied. This study sought to evaluate the efficacy of sublingual immunotherapy with house dust mite extract in children and adults with house dust mite allergic rhinitis over a period of two years.

    METHODS: A prospective observational study was conducted of children and adults diagnosed with house dust mite allergic rhinitis who were treated with sublingual immunotherapy from 2008 to 2012. Total Nasal Symptom Scores, Mini Rhinoconjunctivitis Quality of Life scores and medication usage scores were assessed prospectively.

    RESULTS: Thirty-nine patients, comprising 24 children and 15 adults, were studied. Total Nasal Symptom Scores and Mini Rhinoconjunctivitis Quality of Life scores dropped significantly at three months into therapy, and continued to improve. Medication usage scores improved at one year into immunotherapy.

    CONCLUSION: Sublingual immunotherapy with house dust mite extracts, including B tropicalis, is efficacious as a treatment for patients with house dust mite allergic rhinitis.

    Matched MeSH terms: Sublingual Immunotherapy/methods*
  10. Fulltext Targeting dendritic cells through gold nanoparticles: A review on the cellular uptake and subsequent immunological properties
    Ahmad S, Zamry AA, Tan HT, Wong KK, Lim J, Mohamud R
    Mol Immunol, 2017 11;91:123-133.
    PMID: 28898717 DOI: 10.1016/j.molimm.2017.09.001
    Gold nanoparticles (NPs) have been proposed as a highly potential tool in immunotherapies due to its advantageous properties including customizable size and shapes, surface functionality and biocompatibility. Dendritic cells (DCs), the sentinels of immune response, have been of interest to be manipulated by using gold NPs for targeted delivery of immunotherapeutic agent. Researches done especially in human DCs showed a variation of gold NPs effects on cellular uptake and internalization, DC maturation and subsequent T cells priming as well as cytotoxicity. In this review, we describe the synthesis and physiochemical properties of gold NPs as well as the importance of gold NPs in immunotherapies through their actions on human DCs.
    Matched MeSH terms: Immunotherapy/methods*
  11. Immunotherapies for Parkinson's Disease: Progression of Clinical Development
    Teng JS, Ooi YY, Chye SM, Ling APK, Koh RY
    CNS Neurol Disord Drug Targets, 2021;20(9):802-813.
    PMID: 34042040 DOI: 10.2174/1871527320666210526160926
    Parkinson's disease is a common neurodegenerative disease affecting the movement and well-being of most elderly. The manifestations of Parkinson's disease often include resting tremor, stiffness, bradykinesia, and muscular rigidity. The typical hallmark of Parkinson's disease is the destruction of neurons in the substantia nigra and the presence of Lewy bodies in different compartments of the central nervous system. Due to various limitations to the currently available treatments, immunotherapies have emerged to be the new approach to Parkinson's disease treatment. This approach shows some positive outcomes on the efficacy by removing the aggregated species of alpha-synuclein, which is believed to be one of the causes of Parkinson's disease. In this review, an overview of how alpha-synuclein contributes to Parkinson's disease and the effects of a few new immunotherapeutic treatments, including BIIB054 (cinpanemab), MEDI1341, AFFITOPE, and PRX002 (prasinezumab) that are currently under clinical development, will be discussed.
    Matched MeSH terms: Immunotherapy/methods*
  12. Fulltext Recent advances in nanotheranostics for triple negative breast cancer treatment
    Thakur V, Kutty RV
    J Exp Clin Cancer Res, 2019 Oct 28;38(1):430.
    PMID: 31661003 DOI: 10.1186/s13046-019-1443-1
    Triple-negative breast cancer (TNBC) is the most complex and aggressive type of breast cancer encountered world widely in women. Absence of hormonal receptors on breast cancer cells necessitates the chemotherapy as the only treatment regime. High propensity to metastasize and relapse in addition to poor prognosis and survival motivated the oncologist, nano-medical scientist to develop novel and efficient nanotherapies to solve such a big TNBC challenge. Recently, the focus for enhanced availability, targeted cellular uptake with minimal toxicity is achieved by nano-carriers. These smart nano-carriers carrying all the necessary arsenals (drugs, tracking probe, and ligand) designed in such a way that specifically targets the TNBC cells at site. Articulating the targeted delivery system with multifunctional molecules for high specificity, tracking, diagnosis, and treatment emerged as theranostic approach. In this review, in addition to classical treatment modalities, recent advances in nanotheranostics for early and effective diagnostic and treatment is discussed. This review highlighted the recently FDA approved immunotherapy and all the ongoing clinical trials for TNBC, in addition to nanoparticle assisted immunotherapy. Futuristic but realistic advancements in artificial intelligence (AI) and machine learning not only improve early diagnosis but also assist clinicians for their workup in TNBC. The novel concept of Nanoparticles induced endothelial leakiness (NanoEL) as a way of tumor invasion is also discussed in addition to classical EPR effect. This review intends to provide basic insight and understanding of the novel nano-therapeutic modalities in TNBC diagnosis and treatment and to sensitize the readers for continue designing the novel nanomedicine. This is the first time that designing nanoparticles with stoichiometric definable number of antibodies per nanoparticle now represents the next level of precision by design in nanomedicine.
    Matched MeSH terms: Immunotherapy/methods*
  13. Fulltext Tocotrienols are good adjuvants for developing cancer vaccines
    Hafid SR, Radhakrishnan AK, Nesaretnam K
    BMC Cancer, 2010;10:5.
    PMID: 20051142 DOI: 10.1186/1471-2407-10-5
    Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours.
    Matched MeSH terms: Immunotherapy/methods
  14. The anti-idiotype vaccines for immunotherapy
    Bhattacharya-Chatterjee M, Chatterjee SK, Foon KA
    Curr. Opin. Mol. Ther., 2001 Feb;3(1):63-9.
    PMID: 11249733
    Certain anti-idiotypic antibodies that bind to the antigen-combining sites of antibodies can effectively mimic the three-dimensional structures and functions of the external antigens and can be used as surrogate antigens for active specific immunotherapy. Extensive studies in animal models have demonstrated the efficacy of these vaccines for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections as well as tumors. Several monoclonal anti-idiotype antibodies that mimic distinct human tumor-associated antigens have been developed and characterized. Encouraging results have been obtained in recent clinical trials using these anti-idiotype antibodies as vaccines. In this article, we will review the current literature and discuss the potential of this novel therapeutic approach for various human cancers.
    Matched MeSH terms: Immunotherapy/methods*
  15. Fulltext Human mesenchymal stem cells inhibit the differentiation and effector functions of monocytes
    Maqbool M, Algraittee SJR, Boroojerdi MH, Sarmadi VH, John CM, Vidyadaran S, et al.
    Innate Immun, 2020 07;26(5):424-434.
    PMID: 32635840 DOI: 10.1177/1753425919899132
    Although monocytes represent an essential part of the host defence system, their accumulation and prolonged stimulation could be detrimental and may aggravate chronic inflammatory diseases. The present study has explored the less-understood immunomodulatory effects of mesenchymal stem cells on monocyte functions. Isolated purified human monocytes were co-cultured with human umbilical cord-derived mesenchymal stem cells under appropriate culture conditions to assess monocytes' vital functions. Based on the surface marker analysis, mesenchymal stem cells halted monocyte differentiation into dendritic cells and macrophages and reduced their phagocytosis functions, which rendered an inability to stimulate T-cell proliferation. The present study confers that mesenchymal stem cells exerted potent immunosuppressive activity on monocyte functions such as differentiation, phagocytosis and Ag presentation; hence, they promise a potential therapeutic role in down-regulating the unwanted monocyte-mediated immune responses in the context of chronic inflammatory diseases.
    Matched MeSH terms: Immunotherapy/methods*
  16. Conventional and unconventional therapies in typical and atypical chronic inflammatory demyelinating polyneuropathy with different clinical course of progression
    Hung SKY, Hiew FL, Viswanathan S, Puvanarajah S
    J Peripher Nerv Syst, 2018 Sep;23(3):183-189.
    PMID: 30027593 DOI: 10.1111/jns.12282
    Intravenous immunoglobulin (IVIG), corticosteroids and therapeutic plasma exchange (TPE) are evidence-based conventional treatments for chronic inflammatory demyelinating polyneuropathy (CIDP). In many centres, unconventional treatments are frequently used as alternatives. We evaluated the outcome of conventional and unconventional therapies in 31 CIDP patients. Overall response rate with conventional first-line immunotherapies was 77% (20/26), comparable between IVIG and corticosteroids (80% vs 70%). Use of TPE was limited. Treatment response among typical and atypical CIDP were comparable (76 vs 80%). Non-responders were patients with progressive form of typical CIDP and DADS. Majority (21/26, 81%) of patients with persistent neurological deficits received maintenance therapy. Two subgroups of patients frequently treated with maintenance immunosuppressants were those with improving or stable disease following first-line treatment (12, 57%) and those with progressive form of CIDP (2, 10%). Primary indications for immunosuppressant use were corticosteroids-sparing and additional immunosuppression effects. Nine (64%) patients with improving or stable disease given azathioprine were taken off corticosteroids after a median duration of 14 months (range 12-108). Two (14%) eventually achieved cure or clinical remission without treatment. Maintenance IVIg was given to 6 (29%) relapsing CIDP patients; none of achieved cure or remission after similar median duration of treatment. Less potent immunosuppressant drugs (azathioprine, mycophenolate mofetil, and methotrexate) were frequently used, with moderate adverse effect profiles. In resource limited setting, unconventional treatments were commonly used among CIDP patients with different clinical course of progression. In most cases, careful risk-benefit re-assessment is required to justify its further use.
    Matched MeSH terms: Immunotherapy/methods*
  17. Fulltext Conformational IgE Epitope Mapping of Der p 2 and the Evaluations of Two Candidate Hypoallergens for Immunotherapy
    Reginald K, Chew FT
    Sci Rep, 2018 02 21;8(1):3391.
    PMID: 29467434 DOI: 10.1038/s41598-018-21792-1
    Epitope mapping of Der p 2, a clinically important dust-mite allergen is the first step in designing immunotherapy hypoallergen vaccine candidates. Twenty-one single alanine mutants of Der p 2 were generated and their secondary structure was analysed using circular dichroism spectra. Only one mutant, K96A resulted in a misfolded protein. All mutants were tested for serum IgE reactivity using serum from dust mite allergic individuals by immuno dot-blots. Mutations to five residues, N10, E25, K77, K96 and E102 consistently showed reduced IgE reactions compared to wild-type Der p 2, and therefore these residues constitute the major IgE epitopes of Der p 2. Two mutants with consistent low IgE binding, K96A and E102A, were subsequently evaluated as hypoallergen candidates. IgG antibodies raised in mice against both mutants could inhibit human IgE-binding to WT Der p 2. Both mutants had intact T-cell epitopes as they were able to stimulate peripheral blood mononuclear cell proliferation similar to WT Der p 2. However, a switch in Th1:Th2 cytokine profile was not observed. In summary, we have identified the major conformational epitopes of Der p 2, and evaluated two Der p 2 hypoallergen vaccine candidates for immunotherapy.
    Matched MeSH terms: Immunotherapy/methods
  18. Fulltext Role of Interferons in the Development of Diagnostics, Vaccines, and Therapy for Tuberculosis
    Chin KL, Anis FZ, Sarmiento ME, Norazmi MN, Acosta A
    J Immunol Res, 2017;2017:5212910.
    PMID: 28713838 DOI: 10.1155/2017/5212910
    Tuberculosis (TB) is an airborne infection caused by Mycobacterium tuberculosis (Mtb). About one-third of the world's population is latently infected with TB and 5-15% of them will develop active TB in their lifetime. It is estimated that each case of active TB may cause 10-20 new infections. Host immune response to Mtb is influenced by interferon- (IFN-) signaling pathways, particularly by type I and type II interferons (IFNs). The latter that consists of IFN-γ has been associated with the promotion of Th1 immune response which is associated with protection against TB. Although this aspect remains controversial at present due to the lack of established correlates of protection, currently, there are different prophylactic, diagnostic, and immunotherapeutic approaches in which IFNs play an important role. This review summarizes the main aspects related with the biology of IFNs, mainly associated with TB, as well as presents the main applications of these cytokines related to prophylaxis, diagnosis, and immunotherapy of TB.
    Matched MeSH terms: Immunotherapy/methods
  19. Systemic anti-CTLA-4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism?
    Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G
    Med Hypotheses, 2016 Jul;92:57-8.
    PMID: 27241256 DOI: 10.1016/j.mehy.2016.04.037
    Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.
    Matched MeSH terms: Immunotherapy/methods
  20. Fulltext Experimental production of clinical-grade dendritic cell vaccine for acute myeloid leukemia
    Tan YF, Sim GC, Habsah A, Leong CF, Cheong SK
    Malays J Pathol, 2008 Dec;30(2):73-9.
    PMID: 19291915 MyJurnal
    Dendritic cells (DC) are professional antigen presenting cells of the immune system. Through the use of DC vaccines (DC after exposure to tumour antigens), cryopreserved in single-use aliquots, an attractive and novel immunotherapeutic strategy is available as an option for treatment. In this paper we describe an in vitro attempt to scale-up production of clinical-grade DC vaccines from leukemic cells. Blast cells of two relapsed AML patients were harvested for DC generation in serum-free culture medium containing clinical-grade cytokines GM-CSF, IL-4 and TNF-alpha. Cells from patient 1 were cultured in a bag and those from patient 2 were cultured in a flask. The numbers of seeding cells were 2.24 x 10(8) and 0.8 x 10(8), respectively. DC yields were 10 x 10(6) and 29.8 x 10(6) cells, giving a conversion rate of 4.7% and 37%, respectively. These DC vaccines were then cryopreserved in approximately one million cells per vial with 20% fresh frozen group AB plasma and 10% DMSO. At 12 months and 21 months post cryopreservation, these DC vaccines were thawed, and their sterility, viability, phenotype and functionality were studied. DC vaccines remained sterile up to 21 months of storage. Viability of the cryopreserved DC in the culture bag and flask was found to be 50% and 70% at 12 months post cryopreservation respectively; and 48% and 67% at 21 months post cryopreservation respectively. These DC vaccines exhibited mature DC surface phenotypic markers of CD83, CD86 and HLA-DR, and negative for haemopoietic markers. Mixed lymphocyte reaction (MLR) study showed functional DC vaccines. These experiments demonstrated that it is possible to produce clinical-grade DC vaccines in vitro from blast cells of leukemic patients, which could be cryopreserved up to 21 months for use if repeated vaccinations are required in the course of therapy.
    Matched MeSH terms: Immunotherapy/methods*
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