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TOPICS
Basics | vaccines | Enhancing Vaccines | Rituxan & Other Monoclonal Antibodies
other | Review Articles
In the News:
Basics of Immunotherapy
Background: Immunotherapy: Using the Immune System to Treat Cancer - National Cancer Institute http://bit.ly/2tA44gT
Trends in Cancer Immunotherapy http://bit.ly/cz67Ai
NOTE: The risks and benefits of different immunotherapies are likely to be specific to the type of lymphoma. That is, what is effective / safe for one type may or may not be for another type.
This includes:
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Monoclonal antibodies (page 7)
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Vaccines (page 10)
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T cell infusion (top of page 12)
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Immunomodulators (page 13)
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Vaccines and Other Immune-based therapies
Vaccine treatments are investigational. The goal of this treatment is to induce an immune response against tumor-specific antigens (proteins that only exist on the tumor.) This is sometimes called active immunity.
 TOPIC SEARCH: PubMed: Treatment | Review | Dendritic | Idiotype | DNA type | Heat Shock type
By site: ASCO | ASH | ClinicalTrials.gov | Medscape | Web
By authors: Bendandi | Levy | Timmerman
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Idiotype vaccines
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CD40L-transduced tumor cells as a vaccine Briones, Timmerman, Levy
In vivo anti-tumor effect of CD40L-transduced tumor cells as a vaccine for B-cell lymphoma.
Cancer Res. 2002 Jun 1;62(11):3195-9. PMID: 12036933 PubMed
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Cancer vaccines fact sheet cancer.gov
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Investigational vaccine for cutaneous lymphomas: transgene.fr | ClinicalTrials.gov
TG 1042's antitumoral activity relies on the secretion of human IFNγ from tumor cells adenovirally-transduced with the nucleotidic sequence encoding the cytokine. IFNγ is a natural immunostimulant produced in the body, whose antitumoral properties were demonstrated both in animals and in humans.
...a high rate of local clinical responses : 55% of 31 evaluable patients responded to the treatment with nine complete responses (CR) and eight partial responses (PR). Out of the 26 patients with cutaneous T-cell lymphoma (CTCL) 46% responded (six CR and six PR), and 100% of the five patients with cutaneous B-cell lymphoma (CBCL) responded to the TG1042 treatment (three CR and two PR) :
These results suggest that intralesional therapy with TG 1042 represents a non-toxic and effective treatment for CBCL.
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Fusion-cell vaccines: Patients' Cells From Tumors, The Immune System Merged For Customized Cancer Therapy sciencedaily.com /2004 | PubMed Topic Search
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Harvesting and handling tissue in preparation for vaccines PAL
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Heat shock Protein vaccine - Safety and efficacy of heat shock protein-peptide 96 complex (HSPPC-96)
in low-grade lymphoma. ASCO
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About: Antigenics | aacrjournals.org
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Hybridoma Id Vaccine Results - Overview - Biovest Cancer Vaccine accentia.net
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Treating cancer with vaccines cancer.gov
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A New Vaccine Paradigm To Break Tolerance with Potential Applications for the Immunotherapy of B Cell Lymphoma. Session Type: Poster Session 565-I ASH 2004
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Trioma vaccines - potentially more potent, easier to make, and for more cancers Related PubMed Abstracts
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Viral fusogenic membrane glycoproteins (FMG) related abstracts | cancerres.aacrjournals.org
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Investigational approaches to enhance vaccines:
(overcome tolerance and ways tumors escape)
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Testing Lirilumab With Rituximab for Relapsed, Refractory or High-risk Untreated Chronic Lymphocytic Leukemia (CLL) http://1.usa.gov/1Djdng9
Search of: Lirilumab | lymphoma OR CLL - List Results - ClinicalTrials.gov http://1.usa.gov/1LcQMtK
Poster: Phase 1 dose-escalation study of lirilumab (IPH2102, BMS-986015, LIRI),
a fully human anti-KIR monoclonal antibody in patients with various hematologic (HEM) or solid (SOL) malignancies http://bit.ly/1TFc9Fl
"The blockade of KIR by LIRI fosters the activation of NK cells, selectively enhancing the cytotoxicity of NK cells against tumor cells without affecting healthy tissues."
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NKT cell-targeted vaccination given with 4-1BB leads to CD8 T cell immunity against B cell lymphoma. http://1.usa.gov/1MuMY4c
* Testing PF-05082566 (anti-4-1BB antibody) As A Single Agent and With Rituximab - ClinicalTrials.gov http://1.usa.gov/1e1hKWk
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Can we enhance cancer vaccines? Imatinib mesylate (STI-571) enhances antigen-presenting cell function and overcomes tumor-induced CD4+ T-cell tolerance. Blood. 2005 Feb 1;105(3):1135-43. Epub 2004 Sep 28. PMID: 15454486 | Related articles
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Scientists overcome immune resistance in dendritic cell vaccines for cancer ~ 05 Apr 2004 medicalnewstoday.com
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anti-CTLA-4 - to optimize active immunity Related abstracts
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Boosting Mabs and vaccines? CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins. Eur J Immunol. 2000 Dec;30(12):3591-7. Related abstracts
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CPG-7909 (PF-3512676, ProMune®): toll-like receptor-9 agonist in cancer therapy expertopin.com
Stimulation of toll-like receptor (TLR)9 activates human plasmacytoid dendritic cells and B cells, and induces potent innate immune responses in preclinical tumor models and in patients. CpG oligodeoxynucleotides (ODNs) are TLR9 agonists that show promising results as vaccine adjuvants and in the treatment of cancers, infections, asthma and allergy.
Related studies: ClinicalTrials.gov
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Revlimid (Lenalidomide) - for MDS
The mechanism of action is not yet fully characterized. Lenalidomide possesses immunomodulatory and antiangiogenic properties. It inhibited the secretion of pro-inflammatory cytokines and increased the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. ClinicalTrils.gov
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Adoptive immunotherapy for indolent NHL and MCL using genetically modified autologous
[from self] CD20-specific T cells
Of the 7 treated patients, 2 maintained a previous complete response,
1 achieved a partial response, and 4 had stable disease.
These results show the safety, feasibility, and potential antitumor activity of adoptive T-cell therapy using this approach. This trial was registered at Clinicaltrials.gov NCT00012207
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Therapeutic vaccination against murine lymphoma by intratumoral injection of naive dendritic cells.
Cancer Res. 2005 Jul 1;65(13):5958-64. PMID: 15994975 | Related articles
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Rituxan and Other Monoclonal Antibodies
TOPIC SEARCH: Antibodies | Bispecific Antibodies
Rituxan is an antibody that is thought to have more than one mechanism of action, two of which are dependant on immunity. These are ADCC and CDC which we describe below. These immune mechanisms are referred to as passive immunity:
Antibody-dependent cell-mediated cytotoxicity (ADCC) - depends on the presence of antibodies (Abs) that recognize a target cell (ADCC specificity is therefore conferred by the specificity of the antibody). Upon binding its antigen (Ag), the Antibody's Fc region is exposed and will bind its receptor on the NK cell to form a bridge. Once the bridge is formed, a poorly understood lytic (killing) signal is delivered to the target cell, resulting in its demise. - (adapted from the Merck Manual) Picture-it
Complement-dependent cytotoxicity (CDC): A mechanism of killing cells in which antibody bound to the target cell surface fixes complement, which results in assembly of the membrane attack complex that punches holes in the target cell membrane resulting in subsequent cell lysis. Picture-it
Other Immune-therapy directions
TOPIC SEARCH PubMed: Adenovirus | T-cell Therapy | Bispecific Antibodies
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Adenovirus: Infects lymph node cells isolated from patients with follicle lymphoma so that tumors express proteins that make them more visible to immune cells.
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T cell activation following infection of primary follicle center lymphoma B cells with adenovirus encoding CD154. Leukemia 2001 Sep;15(9):1451-7
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Adenovirus-mediated intralesional (injected inside the tumor) interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas. Blood. 2004 Sep 15;104(6):1631-8. Epub 2004 May 25. PMID: 15161670 | Related articles
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PubMed Abstracts
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Adoptive immunotherapy (T-cell therapy)
"Scientists are exploiting these observations to develop procedures that isolate and expand to great numbers the immune cells responsible for this effect [immune system ability to recognize cancer cells and destroy them] so that the cells can be transfused into patients for cancer treatment." 1
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Adoptive Immunotherapy Fred Hutch Cancer Center
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NEW and promising based on clinical results:
Chimeric Antigen Receptor T-cells (CAR T-cells)
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Cancer T cell therapy expands
` Brian Becknell and Michael A. Caligiuri Nature.com Dec 2004 (subscription req.)
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Safety of Cellular Immunotherapy for CD19+ Follicular Lymphoma Using Autologous T Cell Cytolytic Clones Genetically Modified to be CD19-Speific and Express HyTK - City of Hope Medical Center centerwatch.com
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NK cell adoptive immunotherapy - Andrea Velardi bloodjournal.org
In this issue of Blood, Miller and colleagues present data on the administration of haploidentical NK cells to cancer patients. They identify a feasible and safe method for in vivo NK cell expansion and clinical efficacy.
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T-cell therapy - targeting cd20
A Phase I Trial To Evaluate the Safety of Cellular Immunotherapy using Genetically Modified Autologous CD20-specific CD8+ T Cell Clones for Patients with Relapsed CD20+ Indolent Lymphomas
The study of interest involves taking T-cells from individual patients, genetically altering the cells so that they target CD20 (a receptor found on many b-cell lymphomas and normal b-cells), expanding the numbers, and re-infusing them into the patient following treatment with CVP, a combination of chemotherapy agents.
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T lymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Blood. 2006 Dec 1;108(12):3890-7. Epub 2006 Aug 22.
PMID: 16926291 | Related articles
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T Lymphocyte Therapy of Cancer PDF
"The aim of this article is to review the possibilities, limitations and recent clinical experience with this novel anticancer treatment, namely with adoptive immunotherapy using antigen-specific T cells. "
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Bisphosphonate therapy in multiple myeloma: past, present, future.
Eur J Haematol. 2002 Nov-Dec;69(5-6):257-64. Review. PMID: 12460229 | Abstracts
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Synthetic Phosphoantigens Enhance Human V9V2 T Lymphocytes Killing of
Non-Hodgkin’s B Lymphoma molmed.org (PDF)
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Dipeptidyl peptidase inhibitor (PT-100) ASCO | Related articles
An anti-tumor small molecule that amplifies immunity. Trials running now looking at use with Rituxan.
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Cytokine Therapy
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Interferon-alpha as immune modulation PAL
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anti-CD20-IL2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma. Blood. 2005 Feb 3; PMID: 15692062
This preclinical work appears to be an engineered antibody that binds to cd20 (like rituxan), modified to
interact with IL-2 (a cytokine firmly established as essential to t-cell activation), and modified further to avoid being intercepted by t-cells prior to binding to cd20 cells? Whatever. Amazing assembly.
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Identification of a new HLA-A*0201-restricted cryptic epitope from CYP1B1.
Int J Cancer. 2005 Jun 10;115(2):333-6. PMID: 15688394 | Related articles
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Phase II Clinical Trial of Interleukin-12 in Patients with Relapsed and Refractory Non-Hodgkin’s Lymphoma and Hodgkin’s Disease aacrjournals.org
"The ability of recombinant human IL-12 therapy to increase the number of circulating CD8+ cells and induce clinical remissions in patients with relapsed NHL warrants further investigation of the drug."
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Lenalidomide - "The exact mechanism of the immunomodulatory drugs (i.e. thalidomide, CC-4047/Actimid and lenalidomide) is not known. Apart from interfering with the immune system, they are also thought to act on angiogenesis."
wikipedia.org | ClinicalTrials.gov (Lenalidomide/ Revlimid)
TOPIC SEARCH: Mechanisms PubMed
Outcome ASCO | Medscape | PubMed
Safety ASCO | PubMed
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Measles vaccine Abstract - PubMed
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PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism.
Cancer Res. 2004 Aug 1;64(15):5471-80. PMID: 15289357 | Related articles
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Novel adoptive immunotherapy:
Cancer 'Cure' In Mice To Be Tested In Humans sciencedaily.com | backgrounder
"Leukocyte Infusion Therapy" (LIFT) study information and eligibility
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Review Articles on Immune-based Therapies
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Continuing Medical Education article on Medscape.com intended for practicing physicians: http://cme.medscape.com/viewarticle/720825 (might require a free one-time registration)
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IMMUNOTHERAPY AND CHEMOTHERAPY — A PRACTICAL PARTNERSHIP PDF
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The anticancer immune response: indispensable for therapeutic success? http://bit.ly/4mm0rn
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ASH 2003 Update: Cellular Therapies and Vaccines for Hematologic Malignancies Conference Coverage cancerconsultants.com
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Clinical Trials of Active Immunotherapy in NHL lymphomafocus.org
John P. Leonard, MD - New York Presbyterian Hospital
Ronald Levy, MD - Professor of Medicine, Stanford University Medical Center
David C. Fisher, MD - Instructor of Medicine, Dana-Farber Cancer Institute, Harvard Medical School
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Immunotherapy of B-Cell Malignancies, Gribben Medscape free login req.
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Immunotherapy of Non-Hodgkin's Lymphomas - Oliver W. Press, John P. Leonard, Bertrand Coiffier, Ronald Levy and John Timmerman HTM
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Monoclonal Antibody Therapy for Non-Hodgkin's Lymphoma, Sledge Jr, MD, and Plante Medscape free login req.
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Immunotherapy, Past Present and Future medscape (free login req.)
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Immunotherapy w/ autoBMT medscape (free login req.)
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Immunotherapy of malignant diseases: cancer therapy beyond chemotherapy roche.com PDF
Very nice primer on immunity and immunotherapy.
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