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Recent Advances in Cellular Immunotherapy
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Recent Advances in Cellular Immunotherapy

A special issue of Medical Sciences (ISSN 2076-3271). This special issue belongs to the section "Immunology and Infectious Diseases".

Deadline for manuscript submissions: closed (30 November 2013) | Viewed by 57392

Special Issue Editor

Dr. Subramaniam Malarkannan

E-Mail Website
Guest Editor
Laboratory of Molecular Immunology and Immunotherapy, Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Interests: NK cell development and functions; biochemical and genetic analyses of signaling cascades in NK cells; NK cell-mediated epithelial cell regeneration during influenza infections; NK cell-based cellular immunotherapy for patients with hematological malignancies

Special Issue Information

Dear Colleagues,

In the past decade, academic perseverance and industrial fortitudes revolutionized the positive outcome of cancer therapy and thereby tremendously improving the rate of patient survival. Although it has been kept in the back-burner by the success of novel concoctions of pharmacological compounds, in the past two years cellular immunotherapy has made a roaring comeback. Clinicians and basic scientist alike think and desire of combinatorial and individualized therapies where treatment regimens can be customized to fit with the type and stage of tumor growth. More importantly, the promise of cellular immunotherapy can keep the viciousness of the treatment-related side effects in check. Genetically manipulated lymphocytes including T and NK cells are better than ever in clearing and killing tumor cells. Lymphocytes that are made to express antibody-based Chimeric Antigen Receptor (CAR) function with a significantly higher affinity compared to using their native receptors. Addition of critical cytokines and their receptors in the mix has realigned the basic immunological rules, resulting in a stronger lymphocyte response against malignancies. Although we can feel the excitement about the recent success in cellular immunotherapy methods on the lab benches and hospital beds, they are yet to reach their prime and still have their perils. Cytokine-release syndrome is a major unwanted side effect that we counter when we genetically amplify the immune response. In the first issue of Medical Sciences, we would like to provide a detailed account of the recent advances made in cellular immunotherapy. The good, the worthy and the bad of cellular immunotherapy in one issue!

Dr. Subramaniam Malarkannan
Guest Editor

Manuscript Submission Information

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Keywords

  • cellular immunotherapy
  • genetically modified T and NK cells
  • chimeric antigen receptors
  • genetic manipulation and generation of novel
  • high affinity antigen receptors
  • tumor antigens
  • cytokines and cytokine receptors
  • co-stimulatory receptors
  • altering signaling cascades in lymphocytes
  • cytokine-release syndrome

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Published Papers (6 papers)

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Research

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16 pages, 685 KiB  
Article
NKT Cell Responses to B Cell Lymphoma
by Junxin Li, Wenji Sun, Priyanka B. Subrahmanyam, Carly Page, Kenisha M. Younger, Irina V. Tiper, Matthew Frieman, Amy S. Kimball and Tonya J. Webb
Med. Sci. 2014, 2(2), 82-97; https://doi.org/10.3390/medsci2020082 - 14 Apr 2014
Cited by 15 | Viewed by 8873
Abstract
Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic [...] Read more.
Natural killer T (NKT) cells are a unique subset of CD1d-restricted T lymphocytes that express characteristics of both T cells and natural killer cells. NKT cells mediate tumor immune-surveillance; however, NKT cells are numerically reduced and functionally impaired in lymphoma patients. Many hematologic malignancies express CD1d molecules and co-stimulatory proteins needed to induce anti-tumor immunity by NKT cells, yet most tumors are poorly immunogenic. In this study, we sought to investigate NKT cell responses to B cell lymphoma. In the presence of exogenous antigen, both mouse and human NKT cell lines produce cytokines following stimulation by B cell lymphoma lines. NKT cell populations were examined ex vivo in mouse models of spontaneous B cell lymphoma, and it was found that during early stages, NKT cell responses were enhanced in lymphoma-bearing animals compared to disease-free animals. In contrast, in lymphoma-bearing animals with splenomegaly and lymphadenopathy, NKT cells were functionally impaired. In a mouse model of blastoid variant mantle cell lymphoma, treatment of tumor-bearing mice with a potent NKT cell agonist, α-galactosylceramide (α-GalCer), resulted in a significant decrease in disease pathology. Ex vivo studies demonstrated that NKT cells from α-GalCer treated mice produced IFN-γ following α-GalCer restimulation, unlike NKT cells from vehicle-control treated mice. These data demonstrate an important role for NKT cells in the immune response to an aggressive hematologic malignancy like mantle cell lymphoma. Full article
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
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12 pages, 498 KiB  
Article
In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples
by Ilaria Turin, Roberta Schiavo, Marcello Maestri, Ombretta Luinetti, Barbara Dal Bello, Marco Paulli, Paolo Dionigi, Marianna Roccio, Arsenio Spinillo, Federica Ferulli, Matteo Tanzi, Rita Maccario, Daniela Montagna and Paolo Pedrazzoli
Med. Sci. 2014, 2(2), 70-81; https://doi.org/10.3390/medsci2020070 - 26 Mar 2014
Cited by 4 | Viewed by 9291
Abstract
Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently [...] Read more.
Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines. Full article
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
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19 pages, 3225 KiB  
Article
Characterization of Free and Porous Silicon-Encapsulated Superparamagnetic Iron Oxide Nanoparticles as Platforms for the Development of Theranostic Vaccines
by Charles M. Lundquist, Christopher Loo, Ismail M. Meraz, Jorge De La Cerda, Xuewu Liu and Rita E. Serda
Med. Sci. 2014, 2(1), 51-69; https://doi.org/10.3390/medsci2010051 - 20 Feb 2014
Cited by 2 | Viewed by 13391
Abstract
Tracking vaccine components from the site of injection to their destination in lymphatic tissue, and simultaneously monitoring immune effects, sheds light on the influence of vaccine components on particle and immune cell trafficking and therapeutic efficacy. In this study, we create a hybrid [...] Read more.
Tracking vaccine components from the site of injection to their destination in lymphatic tissue, and simultaneously monitoring immune effects, sheds light on the influence of vaccine components on particle and immune cell trafficking and therapeutic efficacy. In this study, we create a hybrid particle vaccine platform comprised of porous silicon (pSi) and superparamagnetic iron oxide nanoparticles (SPIONs). The impact of nanoparticle size and mode of presentation on magnetic resonance contrast enhancement are examined. SPION-enhanced relaxivity increased as the core diameter of the nanoparticle increased, while encapsulation of SPIONs within a pSi matrix had only minor effects on T2 and no significant effect on T2* relaxation. Following intravenous injection of single and hybrid particles, there was an increase in negative contrast in the spleen, with changes in contrast being slightly greater for free compared to silicon encapsulated SPIONs. Incubation of bone marrow-derived dendritic cells (BMDC) with pSi microparticles loaded with SPIONs, SIINFEKL peptide, and lipopolysaccharide stimulated immune cell interactions and interferon gamma production in OT-1 TCR transgenic CD8+ T cells. Overall, the hybrid particle platform enabled presentation of a complex payload that was traceable, stimulated functional T cell and BMDC interactions, and resolved in cellular activation of T cells in response to a specific antigen. Full article
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
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Review

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14 pages, 358 KiB  
Review
Foreign or Domestic CARs: Receptor Ligands as Antigen-Binding Domains
by Donald R. Shaffer, Penghui Zhou and Stephen Gottschalk
Med. Sci. 2014, 2(1), 23-36; https://doi.org/10.3390/medsci2010023 - 28 Jan 2014
Cited by 3 | Viewed by 7334
Abstract
Chimeric antigen receptors (CARs) are increasingly being used in clinical trials to treat a variety of malignant conditions and recent results with CD19-specific CARs showing complete tumor regressions has sparked the interest of researchers and the public alike. Traditional CARs have been generated [...] Read more.
Chimeric antigen receptors (CARs) are increasingly being used in clinical trials to treat a variety of malignant conditions and recent results with CD19-specific CARs showing complete tumor regressions has sparked the interest of researchers and the public alike. Traditional CARs have been generated using single-chain variable fragments (scFv), often derived from murine monoclonal antibodies, for antigen specificity. As the clinical experience with CAR T cells grows, so does the potential for unwanted immune responses against the foreign transgene. Strategies that may reduce the immunogenicity of CAR T cells are humanization of the scFv and the use of naturally occurring receptor ligands as antigen-binding domains. Herein, we review the experience with alternatively designed CARs that contain receptor ligands rather than scFv. While most of the experiences have been in the pre-clinical setting, clinical data is also emerging. Full article
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
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22 pages, 684 KiB  
Review
Antitumor Immunity and Dietary Compounds
by Annalise R. Smith and Samita Andreansky
Med. Sci. 2014, 2(1), 1-22; https://doi.org/10.3390/medsci2010001 - 27 Dec 2013
Viewed by 11521
Abstract
The mechanisms by which natural dietary compounds exert their antitumor effects have been the focus of a large number of research efforts in recent years. Induction of apoptosis by inhibition of cell proliferative pathways is one of the common means of cell death [...] Read more.
The mechanisms by which natural dietary compounds exert their antitumor effects have been the focus of a large number of research efforts in recent years. Induction of apoptosis by inhibition of cell proliferative pathways is one of the common means of cell death employed by these dietary compounds. However, agents that can activate an antitumor immune response in addition to a chemotherapeutic effect may be useful adjuvants or alternative therapies for the treatment of cancer. The focus of this review is to highlight representative dietary compounds, namely Withania somnifera, Panax ginseng, curcumin and resveratrol with special emphasis on their antitumor immune mechanism of action. Each of these dietary compounds and their sources has a history of safe human use as food or in herbal medicine traditions, potentially making them ideal therapeutics. Here we report the recent advances in the cellular immune mechanisms utilized by these compounds to induce antitumor immunity. Taken together, these findings provide a new perspective for exploiting novel dietary compounds as chemoimmunotherapeutic anti-cancer agents. Full article
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
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12 pages, 989 KiB  
Review
Cellular Immunotherapy: Using Alloreactivity to Induce Anti-Leukemic Responses without Prolonged Persistence of Donor Cells
by Loren D. Fast, John Reagan and Peter Quesenberry
Med. Sci. 2013, 1(1), 37-48; https://doi.org/10.3390/medsci1010037 - 15 Nov 2013
Viewed by 6176
Abstract
A goal of cancer immunologists is to harness cellular immune responses to achieve anti-cancer responses. One of the strongest activating stimuli for the immune system is the encounter with cells expressing allogeneic HLA molecules. While alloreactive responses can negatively impact of the outcome [...] Read more.
A goal of cancer immunologists is to harness cellular immune responses to achieve anti-cancer responses. One of the strongest activating stimuli for the immune system is the encounter with cells expressing allogeneic HLA molecules. While alloreactive responses can negatively impact of the outcome of hematopoietic stem cell transplant because of graft-versus-host disease (GVHD), these same responses can have anti-leukemic effects. Donor lymphocyte infusions have been used in an attempt to harness alloreactive responses to achieve anti-leukemic responses. Because this protocol is usually carried out in the absence of recipient anti-donor responses, this protocol often induces GVHD as well as anti-leukemic responses. A recent study indicated the infusion of large number of haploidentical donor cells (1–2 × 108 CD3+ cells/kg) into patients with refractory hematological malignancies (100 cGy total body irradiation) resulted in 14 (7 major) responses/26 patients. A rapidly developing cytokine storm was observed, while no persisting donor cells could be detected at two weeks after infusion eliminating the possibility of GVHD. Characterization of the effector mechanisms responsible for the anti-leukemic responses in this protocol, should guide new approaches for achieving enhanced anti-leukemic responses using this protocol. Full article
(This article belongs to the Special Issue Recent Advances in Cellular Immunotherapy)
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