1) Treatment with cyclophosphamide induces expansion of immature dendritic cells in the peripheral blood peaking at day 12 post-treatment.
2) These dendritic cells demonstrate phagocytic and antigen presentation capabilities, indicating their biological function.
3) Triggering toll-like receptors on the expanded dendritic cells via specific agonists induces trafficking of dendritic cells to lymph nodes and increases the expansion and anti-tumor efficacy of adoptively transferred CD8+ T cells when combined with peptide vaccination.
The document discusses control system trends and different distributed control system (DCS) architectures. It describes the evolution of DCS from centralized to distributed control with fieldbus connectivity. It provides examples of DCS installations and components of DCS systems from manufacturers like Honeywell, Yokogawa, and ABB. These include control stations, input/output modules, networks, and the use of Windows-based control.
هذا العرض يركز علي قانون حوافز العلوم والإبتكار الذي أطلقته الدولة لنشاء شركات من منتجات البحث العلمي في الجامعات
تم القاء هذه المحاضرة في المنتسي السنوي للبيئة بكلية العلوم امعة طنطا
COVID-19 and Immunity The 21th Threat, By Prof. Mohamed Labib Salem, PhD
Prof. of Immunology, Faculty of Science
Director, Center of Excellence in Cancer Research, Tanta University, Egypt
Talk outlines
Historical Pandemic outbreaks
Basics of Coronavirus and COVID-19
Immune Responses to the new Coronavirus
Anti-Coronavirus treatments
My contribution
This lecture was presented at the Faculty of Science, Tanta University to undergraduate students during the 1st forum organized by Tanta University Scientific Society (TSSS), October 2021
This lecture was presented online on November 6, 2021, in response to an invitation by the Zoology Department, Faculty of Science, Suez Canal University, Egypt
Scientists but Writers by Prof. Mohamed Labib Salem, Tanta University, EgyptProf. Mohamed Labib Salem
علماء ولكن أدباء
ا.د. محمد لبيب سالم
أستاذ علم المناعة بكلية العلوم جامعة طنطا
كاتب وروائي وعضو اتحاد كتاب مصر
بدعوة من الجامعة المصرية اليابانية
21 June 2021
The document discusses control system trends and different distributed control system (DCS) architectures. It describes the evolution of DCS from centralized to distributed control with fieldbus connectivity. It provides examples of DCS installations and components of DCS systems from manufacturers like Honeywell, Yokogawa, and ABB. These include control stations, input/output modules, networks, and the use of Windows-based control.
هذا العرض يركز علي قانون حوافز العلوم والإبتكار الذي أطلقته الدولة لنشاء شركات من منتجات البحث العلمي في الجامعات
تم القاء هذه المحاضرة في المنتسي السنوي للبيئة بكلية العلوم امعة طنطا
COVID-19 and Immunity The 21th Threat, By Prof. Mohamed Labib Salem, PhD
Prof. of Immunology, Faculty of Science
Director, Center of Excellence in Cancer Research, Tanta University, Egypt
Talk outlines
Historical Pandemic outbreaks
Basics of Coronavirus and COVID-19
Immune Responses to the new Coronavirus
Anti-Coronavirus treatments
My contribution
This lecture was presented at the Faculty of Science, Tanta University to undergraduate students during the 1st forum organized by Tanta University Scientific Society (TSSS), October 2021
This lecture was presented online on November 6, 2021, in response to an invitation by the Zoology Department, Faculty of Science, Suez Canal University, Egypt
Scientists but Writers by Prof. Mohamed Labib Salem, Tanta University, EgyptProf. Mohamed Labib Salem
علماء ولكن أدباء
ا.د. محمد لبيب سالم
أستاذ علم المناعة بكلية العلوم جامعة طنطا
كاتب وروائي وعضو اتحاد كتاب مصر
بدعوة من الجامعة المصرية اليابانية
21 June 2021
By Mohamed Labib Salem, PhD
Prof. of ImmunologyFaculty of Science, Tanta University, Egypt
The Scientific Conference on Laboratory Diagnosis and ICSI
المؤتمر العلمى الدولى
للحقن المجهرى والتشخيص المعملى
15 March 2013, Damanhur, Egypt
The Route to Research Fundraising: Tanta University as a Success Story ;By: P...Prof. Mohamed Labib Salem
Prof. Mohamed L. Salem presented on Tanta University's success in research fundraising. Key points include:
- Tanta University established the Grants, Innovation & Technology Transfer Center to support research projects and capacity building.
- Funding for research projects at Tanta University has increased from local and international sources like STDF, reaching over 35 million Egyptian pounds from 2010-2014.
- A major project was the Center of Excellence in Cancer Research funded by an STDF grant, which established advanced equipment and aims to perform translational cancer research.
Egypt: The Beating Heart of The World (By Prof. Mohamed Labib Salem, China, 2...Prof. Mohamed Labib Salem
By DR. Mohamed Labib Salem, PhD
Prof. of Immunology
Zoology Department, Faculty of Science
Director, Competitive Project Unit
Tanta University, Egypt
Presented to:
The Student Union of the Institute of Biophysics
Chinese Academy of Sciences
Beijing, China
February 23, 2012
How to Establish Animal Core Facility (VIVARIUM) by Prof. Mohamed Labib Salem...Prof. Mohamed Labib Salem
By Dr. Mohamed L. Salem, PhD
Prof. of Immunology
Zoology Department, Faculty of Science, Tanta University, Egypt
Presented at the AEAS Annual Conference of AEAS, Cairo
December 18, 2006
Cellular and Molecular Tumor Markers by Prof. Mohamed Labib Salem, PhD (Lux...Prof. Mohamed Labib Salem
This document provides an overview of cellular and molecular tumor markers. It discusses what cancer and tumors are, different types of tumor markers including cellular markers, and applications of tumor markers such as detection, diagnosis and monitoring treatment response. Evaluation criteria for tumor markers like sensitivity and specificity are covered. Common tumor markers used for specific cancer types are listed. Methods for measuring tumor markers like ELISA, PCR, immunohistochemistry and mass spectrometry are described. Limitations of tumor markers are also noted.
This document outlines the basic steps in cancer research. It discusses how cancer cells differ from normal cells by invading surrounding tissues and spreading to other sites. There are different types of cancer like oral, liver, and skin cancer. Cancer research involves epidemiology, prediction, prevention, early detection, diagnosis, prognosis, and treatment methods like surgery, chemotherapy, radiation, and immunotherapy. Research goes through different phases from students to professors and uses various skills, methods, and readouts to analyze effects on tumors and immune responses in vitro, ex vivo, and in vivo using animal tumor models. The overall goal is to translate findings from preclinical research in the lab through clinical trials to benefit patients.
Fostering The Roles of Universities In Implementing The Sustainable Developm...Prof. Mohamed Labib Salem
Fostering The Roles of Universities In Implementing The Sustainable Development of The Surrounding Community
By Prof. Mohamed Labib Salem, PhD
Professor of Immunology
Faculty of Science, Tanta University, Egypt
Presented at:
Presented at the 2nd Int. Environment Forum:
New Environmental Horizons of Sustainable Environment
27-29 November 2008, Tanta University, Egypt
Chemotherapy Friends or Foe to Cancer Immunotherapy by Prof. Mohamed L. SalemProf. Mohamed Labib Salem
This talk is presented by Mohamed Labib Salem, Ph.D.; Prof. of Immunology; Director, Center of Excellence in Cancer Research, Tanta University, Egypt
at the 15TH INTERNATIONAL CONFERENCE ON CHEMISTRY AND ITS ROLE IN DEVELOPMENT (15TH ICCRD), August 9, 2021
Faculty of Science, Mansoura University, Egypt
In vitro fertilization (IVF) and immunotherapy by Prof. Mohamed Labib Salem, ...Prof. Mohamed Labib Salem
This document discusses immunological factors that can impact in vitro fertilization (IVF) success rates. It notes that maternal immune tolerance is required for pregnancy but may be insufficient in some cases, leading to issues like miscarriage. IVF is an alternative to bypass some fertility issues but has limitations. Immunological testing and immunotherapy during IVF, like treating certain antibodies, has increased IVF success rates to 40-50%, compared to typical averages. Precise microinjection techniques are important for IVF/ICSI procedures. Overall, considering immunological factors can improve IVF outcomes for patients with recurrent implantation failure or pregnancy loss.
This document provides an overview of immunogenetics. It begins with an agenda that defines immunogenetics and discusses immune responses, diversity mechanisms, and immunodeficiency diseases. The document then defines immunogenetics as the study of genetic control of immune cells and molecules. It focuses on structure and organization of immune response genes, HLA antigens and disease association, generation of antibody and T cell diversity. Mechanisms creating diversity for B cell receptors, T cell receptors and HLA are described. Finally, immunodeficiency diseases associated with impaired immune function are briefly discussed.
Trans disciplinary research is a must for excellence in science by Prof. Moha...Prof. Mohamed Labib Salem
In this talk, Prof. Mohamed L. Salem presents the importance of having a center of excellence at each institute to enhance and foster scientific research and innovation.
Biotechnology and lab. animals by Prof. Mohamed Labib Salem, Tamta UniversityProf. Mohamed Labib Salem
In this lecture, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt presents information on the role of animals in proofing ideas in bench and make it available to clinical trials. The lecture van useful for both undergraduate and postgraduate students in genetics, molecular biology and biomedical sector.
Immune Responses To The Pandemic New Coronavirus (COVID-19)by Prof. Mohamed L...Prof. Mohamed Labib Salem
In response to an invitation from Benha University, in this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt, presents entitled "Immune Responses To The Pandemic New Coronavirus (COVID-19)".
في هذه المحاضرة يقدم يا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر محاضرة عن فيروس كورونا والمناعة
Dros africa the role of center of excellence in fostering scientific research...Prof. Mohamed Labib Salem
In this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt presents Dross Africa the role of center of excellence in fostering scientific research in Africa.
في هذه المحاضرة والتي كانت بدعوة من هيئة بحثية من الاتحاد الأوروبي يقدم ا.د. محمد ابيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر اهمية انشاء مراكز التميز في العلمي في تقدم . البحث العلمي وخاصة في قارة افريقيا ثم يقدم ثلاث مراكز تميز تم انشائهم في جامعة طنطا كمثال واقعي وقصص نجاح. هذه المراكز الثلاث هي مركز التميز لابحاث السرطان ومركز البصمة الجينية للسرطان ومركز ابحاث وعلاج الثلاثليهميا
Signaling mechanisms in nobel research pathway by Prof. Mohamed Labib Salem, ...Prof. Mohamed Labib Salem
In this lecture, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt presents basic information on Nobel Prize, including history, rules, and winners. He also provides a pathway to young researchers to reach Nobel research that can lead to Nobel Prize.
في هذه المحاضرة يقدم ا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا بمصر طريق النجاح في البحث العلمي الذي قد يؤدي إلي جائزة نوبل في العلوم.
The role of teaching basic science in advancing applied science by Prof. Moha...Prof. Mohamed Labib Salem
Applied science in Egypt, in particular, Medical Education has been facing serious challenges. In this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta, University, Egypt presents a lecture on the role of teaching basic science in advancing applied science. He will discuss how the basic science sector is critical for the success, promotion, and sustainability of medical sector education. He will also discuss how the Flexor report in the USA in 1908 enhanced medical education in the USA.
بدعوة كريمة من مجلس سياسيات التعليم بأكاديمية البحث العلمي والتكنولوجيا يقدم ا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر هذه المحاضرة مقترح عن اهمية ادراج تعليم العلوم الاساسية في تطوير تدريس العلوم الطبية
مجموعة من الخطوات الأساسية للحصول علي منح دراسية لجميع مراحل الدراسات العليا بالخارج من خلال مواقع البحث المعروفة . تم القاء هذه المحاضرة في كلية العلوم جامعة طنطا من قبل ا.د. محمد لبيب سالم رئيس مجلس إدارة الجمعية المصرية لأبحاث السرطان ضمن فعاليات ندوة مفتوحة للباحثين .
A lecture by Mohamed Labib Salem: Teaching versus research in academia a symb...Prof. Mohamed Labib Salem
Presented at The 35th Conference of the Association of Egyptian American Scholars: Cooperation among Scholars in Egypt and Abroad: Strategies and a Vision for Modern Education
December 27-29, 2008, Supreme Council of Universities, Cairo – Egypt
A lecture by by Prof. Mohamed Labib Salem: Fostering The Roles of Universitie...Prof. Mohamed Labib Salem
This talk was presented by Prof. Mohamed Labib Salem at the 2nd Int. Environment Forum: New Environmental Horizons of Sustainable Environment; 27-29 November, 2008, Tanta University, Egypt
محاضرة من ا.د. محمد لبيب سالم
كلية العلوم جامعة طنطا - مصر
By Mohamed Labib Salem, PhD
Prof. of ImmunologyFaculty of Science, Tanta University, Egypt
The Scientific Conference on Laboratory Diagnosis and ICSI
المؤتمر العلمى الدولى
للحقن المجهرى والتشخيص المعملى
15 March 2013, Damanhur, Egypt
The Route to Research Fundraising: Tanta University as a Success Story ;By: P...Prof. Mohamed Labib Salem
Prof. Mohamed L. Salem presented on Tanta University's success in research fundraising. Key points include:
- Tanta University established the Grants, Innovation & Technology Transfer Center to support research projects and capacity building.
- Funding for research projects at Tanta University has increased from local and international sources like STDF, reaching over 35 million Egyptian pounds from 2010-2014.
- A major project was the Center of Excellence in Cancer Research funded by an STDF grant, which established advanced equipment and aims to perform translational cancer research.
Egypt: The Beating Heart of The World (By Prof. Mohamed Labib Salem, China, 2...Prof. Mohamed Labib Salem
By DR. Mohamed Labib Salem, PhD
Prof. of Immunology
Zoology Department, Faculty of Science
Director, Competitive Project Unit
Tanta University, Egypt
Presented to:
The Student Union of the Institute of Biophysics
Chinese Academy of Sciences
Beijing, China
February 23, 2012
How to Establish Animal Core Facility (VIVARIUM) by Prof. Mohamed Labib Salem...Prof. Mohamed Labib Salem
By Dr. Mohamed L. Salem, PhD
Prof. of Immunology
Zoology Department, Faculty of Science, Tanta University, Egypt
Presented at the AEAS Annual Conference of AEAS, Cairo
December 18, 2006
Cellular and Molecular Tumor Markers by Prof. Mohamed Labib Salem, PhD (Lux...Prof. Mohamed Labib Salem
This document provides an overview of cellular and molecular tumor markers. It discusses what cancer and tumors are, different types of tumor markers including cellular markers, and applications of tumor markers such as detection, diagnosis and monitoring treatment response. Evaluation criteria for tumor markers like sensitivity and specificity are covered. Common tumor markers used for specific cancer types are listed. Methods for measuring tumor markers like ELISA, PCR, immunohistochemistry and mass spectrometry are described. Limitations of tumor markers are also noted.
This document outlines the basic steps in cancer research. It discusses how cancer cells differ from normal cells by invading surrounding tissues and spreading to other sites. There are different types of cancer like oral, liver, and skin cancer. Cancer research involves epidemiology, prediction, prevention, early detection, diagnosis, prognosis, and treatment methods like surgery, chemotherapy, radiation, and immunotherapy. Research goes through different phases from students to professors and uses various skills, methods, and readouts to analyze effects on tumors and immune responses in vitro, ex vivo, and in vivo using animal tumor models. The overall goal is to translate findings from preclinical research in the lab through clinical trials to benefit patients.
Fostering The Roles of Universities In Implementing The Sustainable Developm...Prof. Mohamed Labib Salem
Fostering The Roles of Universities In Implementing The Sustainable Development of The Surrounding Community
By Prof. Mohamed Labib Salem, PhD
Professor of Immunology
Faculty of Science, Tanta University, Egypt
Presented at:
Presented at the 2nd Int. Environment Forum:
New Environmental Horizons of Sustainable Environment
27-29 November 2008, Tanta University, Egypt
Chemotherapy Friends or Foe to Cancer Immunotherapy by Prof. Mohamed L. SalemProf. Mohamed Labib Salem
This talk is presented by Mohamed Labib Salem, Ph.D.; Prof. of Immunology; Director, Center of Excellence in Cancer Research, Tanta University, Egypt
at the 15TH INTERNATIONAL CONFERENCE ON CHEMISTRY AND ITS ROLE IN DEVELOPMENT (15TH ICCRD), August 9, 2021
Faculty of Science, Mansoura University, Egypt
In vitro fertilization (IVF) and immunotherapy by Prof. Mohamed Labib Salem, ...Prof. Mohamed Labib Salem
This document discusses immunological factors that can impact in vitro fertilization (IVF) success rates. It notes that maternal immune tolerance is required for pregnancy but may be insufficient in some cases, leading to issues like miscarriage. IVF is an alternative to bypass some fertility issues but has limitations. Immunological testing and immunotherapy during IVF, like treating certain antibodies, has increased IVF success rates to 40-50%, compared to typical averages. Precise microinjection techniques are important for IVF/ICSI procedures. Overall, considering immunological factors can improve IVF outcomes for patients with recurrent implantation failure or pregnancy loss.
This document provides an overview of immunogenetics. It begins with an agenda that defines immunogenetics and discusses immune responses, diversity mechanisms, and immunodeficiency diseases. The document then defines immunogenetics as the study of genetic control of immune cells and molecules. It focuses on structure and organization of immune response genes, HLA antigens and disease association, generation of antibody and T cell diversity. Mechanisms creating diversity for B cell receptors, T cell receptors and HLA are described. Finally, immunodeficiency diseases associated with impaired immune function are briefly discussed.
Trans disciplinary research is a must for excellence in science by Prof. Moha...Prof. Mohamed Labib Salem
In this talk, Prof. Mohamed L. Salem presents the importance of having a center of excellence at each institute to enhance and foster scientific research and innovation.
Biotechnology and lab. animals by Prof. Mohamed Labib Salem, Tamta UniversityProf. Mohamed Labib Salem
In this lecture, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt presents information on the role of animals in proofing ideas in bench and make it available to clinical trials. The lecture van useful for both undergraduate and postgraduate students in genetics, molecular biology and biomedical sector.
Immune Responses To The Pandemic New Coronavirus (COVID-19)by Prof. Mohamed L...Prof. Mohamed Labib Salem
In response to an invitation from Benha University, in this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt, presents entitled "Immune Responses To The Pandemic New Coronavirus (COVID-19)".
في هذه المحاضرة يقدم يا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر محاضرة عن فيروس كورونا والمناعة
Dros africa the role of center of excellence in fostering scientific research...Prof. Mohamed Labib Salem
In this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt presents Dross Africa the role of center of excellence in fostering scientific research in Africa.
في هذه المحاضرة والتي كانت بدعوة من هيئة بحثية من الاتحاد الأوروبي يقدم ا.د. محمد ابيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر اهمية انشاء مراكز التميز في العلمي في تقدم . البحث العلمي وخاصة في قارة افريقيا ثم يقدم ثلاث مراكز تميز تم انشائهم في جامعة طنطا كمثال واقعي وقصص نجاح. هذه المراكز الثلاث هي مركز التميز لابحاث السرطان ومركز البصمة الجينية للسرطان ومركز ابحاث وعلاج الثلاثليهميا
Signaling mechanisms in nobel research pathway by Prof. Mohamed Labib Salem, ...Prof. Mohamed Labib Salem
In this lecture, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta University, Egypt presents basic information on Nobel Prize, including history, rules, and winners. He also provides a pathway to young researchers to reach Nobel research that can lead to Nobel Prize.
في هذه المحاضرة يقدم ا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا بمصر طريق النجاح في البحث العلمي الذي قد يؤدي إلي جائزة نوبل في العلوم.
The role of teaching basic science in advancing applied science by Prof. Moha...Prof. Mohamed Labib Salem
Applied science in Egypt, in particular, Medical Education has been facing serious challenges. In this presentation, Prof. Mohamed Labib Salem, Prof. of Immunology, Faculty of Science, Tanta, University, Egypt presents a lecture on the role of teaching basic science in advancing applied science. He will discuss how the basic science sector is critical for the success, promotion, and sustainability of medical sector education. He will also discuss how the Flexor report in the USA in 1908 enhanced medical education in the USA.
بدعوة كريمة من مجلس سياسيات التعليم بأكاديمية البحث العلمي والتكنولوجيا يقدم ا.د. محمد لبيب سالم أستاذ علم المناعة بكلية العلوم جامعة طنطا مصر هذه المحاضرة مقترح عن اهمية ادراج تعليم العلوم الاساسية في تطوير تدريس العلوم الطبية
مجموعة من الخطوات الأساسية للحصول علي منح دراسية لجميع مراحل الدراسات العليا بالخارج من خلال مواقع البحث المعروفة . تم القاء هذه المحاضرة في كلية العلوم جامعة طنطا من قبل ا.د. محمد لبيب سالم رئيس مجلس إدارة الجمعية المصرية لأبحاث السرطان ضمن فعاليات ندوة مفتوحة للباحثين .
A lecture by Mohamed Labib Salem: Teaching versus research in academia a symb...Prof. Mohamed Labib Salem
Presented at The 35th Conference of the Association of Egyptian American Scholars: Cooperation among Scholars in Egypt and Abroad: Strategies and a Vision for Modern Education
December 27-29, 2008, Supreme Council of Universities, Cairo – Egypt
A lecture by by Prof. Mohamed Labib Salem: Fostering The Roles of Universitie...Prof. Mohamed Labib Salem
This talk was presented by Prof. Mohamed Labib Salem at the 2nd Int. Environment Forum: New Environmental Horizons of Sustainable Environment; 27-29 November, 2008, Tanta University, Egypt
محاضرة من ا.د. محمد لبيب سالم
كلية العلوم جامعة طنطا - مصر
A lecture by by Prof. Mohamed Labib Salem: Fostering The Roles of Universitie...
Prof. Mohamed Labib Sale, AACR Abstract 2008
1. DenDritic cells expanD post cyclophosphamiDe anD meDiate robust anti-tumor responses
upon their stimulation with tlr3 agonist
Mohamed L. Salem, C. Marcela Díaz-Montero, Amir A. AL-Khami , Sabry EL-Naggar, and David J. Cole
Section of Surgical Oncology, Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA
abstract
Numerous preclinical and clinical studies would suggest that pre-conditioning a recipi-
Elimination of Figure 7. Depletion of DCs ab-
cytokine sink Aim
ent host via lymphodepletion can augment adoptive T cell therapy. Although several rogates the augmented T cell
Figure 1. An interactive model for responses post CTX therapy. WT
possibilities have been suggested, the precise mechanisms behind this augmentation
the mechanisms underlying the and DTR Tg mice (3 mice/group)
?
remain elusive. We show herein that treatment of naïve B6 mice with a standard Elimination
Role of
of regulatory impact of lymphodepletion on the were treated with PBS or CTX
lymphodepletion regimen (4 mg cyclophosphamide (CTX)) induces a marked expan-
sion of immature myeloid (CD11chighCD11bhighB220low) dendritic cells (DCs) in the
elements DCs enhanced Ag-specific responses and then adoptively transferred
of adoptively transferred T cells. 1 day later with pmel-1 cells. The
peripheral blood from days 8 to 16 post treatment, (peaking on day 12). In vitro, these
DCs demonstrated phagocytic and effective Ag presentation capability upon stimula- Induction of survival mice were vaccinated with gp100/
cytokines
tion, indicating that they are biologically functional. In vivo, triggering toll-like receptors poly(I:C) on both days 2 and 12
(TLR) by their specific agonists at the peak of DC expansion induced an inflammatory post PBS or CTX treatment. On
milieu and activation of post CTX expanded DCs leading to their trafficking into lymph day 11, the DTR Tg mice were
nodes. Importantly, peptide vaccination combined with TLR3 agonist administration treated i.p. with 90 ng/mouse
at the peak of DC expansion strikingly increased the expansion and the anti-tumor diphtheria toxin to deplete DCs.
efficacy of adoptively transferred naïve pmel-1 CD8+ T cells. These effects were ab-
Models for adoptive T cell transfer The mice were sacrificed 2 days
solutely mediated by DCs. In conclusion, our data suggest that post CTX expansion post re-vaccination to analyze the
of DCs represents a novel mechanism contributing to the augmentation of adoptive numbers of DCs (A and B) and the
T cell therapy by lymphodepletion. Furthermore, these cells could potentially be ex- Finkelstein et al., J Leukoc Biol. 2004;76(2):333-337 expansion of pmel-1 cells (C).
ploited in vivo to foster more effective anti-tumor adoptive immunotherapy strategies.
Figure 5. Interaction of pmel-1 CD8+ transgenic T cells with B16 melanoma. T cells
express a TCR recognizing a H-2Db-restricted CD8+ epitope from the gp100/pmel-17
introDuction protein mouse gp10025–33 (EGSRNQDWL) or human gp10025–33 (KVPRNQDWL).
APC, Antigen-presenting cell. Figure 8. Peptide boosting at
Preconditioning a host with lymphodepletion using either total body irradiation (TBI) or Figure 3. CTX preferentially induced expansion of circulating DC1 expressing imma- [A] [B]
the peak of post CTX DC expan-
450 100
chemotherapy (such as cyclophosphamide (CTX)) regimens can effectively augment ture phenotype. (A) Naïve B6 mice (n=4/group) were i.p. treated with PBS or CTX and 400
350
sion is essential to establish a
80
the anti-tumor efficacy of adoptively transferred T cells.1-6 bled to analyze the DC activation in PBL. (B) Shows the phenotypic characterization 300
therapeutic anti-tumor immunity of
60
250
Suggested mechanisms underlying this effect include: of DC1 (R3 and R5) and DC2 (R4, R6, and R7) gated from R2. (C) Shows the relative 200
self tumor Ag. (A) B6 mice (n=5/
40
Tumor area (mm2) Percent survival
150
1. Enhanced engraftment and survival of the transferred T cells by creation of an numbers of DC1 (CD11chighCD11bhighLy6GlowB220low) and DC2 (CD11chighCD1 100 20
50 group) were challenged with B16
*
immunological “niche” 7 with the induction of survival cytokines. 8, 9 1blowGr.1highB220high) in PBL. (D, left panel) Shows phagocytosis of DCs. (D, right 0 0
9 12 15 18 21 24
tumor and treated with CTX after
27 30 33 10 20 30 40
2. Elimination of the regulatory CD4+CD25+ T (Treg), NKT cells, and myeloid-de- panel) Shows the in vitro Ag presenting function of DCs sorted from PBL of PBS or Days post pmel-1 cell transfer
[C]
Days post pmel-1 cell transfer
10 days. Then, mice were vacci-
CTX treated mice.
No CTX, no pmel
rived suppressor cells. 3, 10-12 CTX alone
nated with gp100/poly(I:C) on day
PBS/Naive pmel-1+gp100/poly(I:C) on day 2
3. Depletion of endogenous cells that compete with the transferred T cells for cytok- 2 or on both day 2 and day 12 post
PBS/Naïve pmel-1+gp100+poly(I:C) on days 2&12
CTX/Naïve pmel-1+gp100/poly(I:C) on day 2
ines (“cytokine sink”) 7, 8, 13 CTX treatment. Two extra groups
CTX/Naïve pmel-1+gp100+poly(I:C) on days 2&12
We have recently reported that the adoptive transfer of T cells early after CTX treat- were challenged with B16 cells
and treated with PBS or CTX. (B)
2 vaccinations 1 vaccination
ment strikingly enhances the post vaccination T cell responses, and that analysis of Figure 1. CTX preconditioning, adoptive T cell transfer, and vaccination. Recipient on days 2 & 12 on day 2
the mechanisms underlying the beneficial effects of CTX showed that.14 WT naïve Ly5.2 mice were treated with PBS or 4mg/mouse CTX and adoptively trans- Survival of the tumor-bearing mice
1. Associated with the induction of the inflammatory cytokines IFN-a, MCP-1, and IL-6. ferred 1 day later by i.v. tail vein injection with 1 million of naive OT-1 or pmel-1 Ly5.1 in (A). (C) Shows vitiligo developed in recipients in (A) vaccinated once or twice.
2. Type I IFNs are critical. cells. The mice were then vaccinated on day 2 and/or 12 with OVAp (in the case of
3. Creation of a space niche was not a critical factor. OT-1 model) or gp100 melanoma peptide (in the case of pmel-1 model) along with
4. Associated with decreases in the numbers of Treg cells. or without poly(I:C). The mice were bled and sacrificed at the indicated time points to conclusions
5. Associated with rapid activation of DCs. (Similarly, activation of DCs was also analyze the expansion and contraction of pmel-1 cells.
CTX treatment results in a significant increase in both the relative and absolute
reported in the mice rendered lymphopenic by TBI due to the systemic release of
numbers of DCs during the restoration phase.
lipopolysaccharide (LPS) after lymphopdepletion3).
Post CTX expanded DCs preferentially express myeloid DC1, immature phenotype.
6. Myeloid (CD11b+) cells were critical.
Post CTX expanded DCs are biologically functional.
Recent studies, in addition to ours, showed that lymphodepletion mechanisms are not Prime-boost with peptide/poly(I:C) at the lymphopenic and restoration (DC expan-
restricted to the homeostatic proliferation of the transferred T cells, the elimination of sion peak) phases post CTX therapy is essential and sufficient to generate and
the endogenous suppressor cells, or the availability of endogenous cytokines 4, 14-17, establish the anti-tumor efficacy of adoptive cell transfer therapy.
indicating that additional unknown mechanisms might exist. Our data indicate that DC expansion represents a novel mechanism behind the
beneficial effects of CTX to adoptive cell transfer therapy.
hypothesis References
Figure 4. Triggering TLR3 signaling at the peak of post CTX DC expansion creates an Figure 6. Stimulation of post CTX expanded DCs induces their migration to LNs aug-
Given the observations of DC activation and the critical role of myeloid cells, we hy- inflammatory milieu, augmenting the Ag-specific CD8+ T cell responses. CTX treated menting CD8+ T cell responses to self tumor Ag. Naïve B6 mice were inoculated with
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post CTX therapy. points post CTX treatment. (B) Shows the absolute numbers of DCs ± SD. Shows the fold increases in the OT-1 expansion in the PBL. PBL (D, left panel) and LNs (D, right panel).
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