Gene and Cellular Immunotherapy for Cancer

The preparation of dendritic cells (DCs) for adoptive cellular immunotherapy (ACI) requires the maturation of ex vivo-produced immature(i) DCs. This maturation ensures that the antigen presentation triggers an immune response towards the antigen-expressing cells. Although there is a large number of maturation agents capable of inducing strong DC maturation, there is still only a very limited number of these agents approved for use in the production of DCs for ACI. In seeking novel DC maturation agents, we used differentially activated human mast cell (MC) line LAD2 as a cellular adjuvant to elicit or modulate the maturation of ex vivo-produced monocyte-derived iDCs. We found that co-culture of iDCs with differentially activated LAD2 MCs in serum-containing media significantly modulated polyinosinic:polycytidylic acid (poly I:C)-elicited DC maturation as determined through the surface expression of the maturation markers CD80, CD83, CD86, and human leukocyte antigen(HLA)-DR. Once iDCs were generated in serum-free conditions, they became refractory to the maturation with poly I:C, and the LAD2 MC modulatory potential was minimized. However, the maturation-refractory phenotype of the serum-free generated iDCs was largely overcome by co-culture with thapsigargin-stimulated LAD2 MCs. Our data suggest that differentially stimulated mast cells could be novel and highly potent cellular adjuvants for the maturation of DCs for ACI.

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Targeting macrophages in cancer immunotherapy

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00506-6 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zhaojun Duan ◽

Yunping Luo

Keyword(s):

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Therapeutic Strategies ◽

Cellular Immunotherapy ◽

Cancer Therapies ◽

Tumor Vaccines ◽

Development And Differentiation ◽

Promising Treatment ◽

Cancer Immunotherapies

AbstractImmunotherapy is regarded as the most promising treatment for cancers. Various cancer immunotherapies, including adoptive cellular immunotherapy, tumor vaccines, antibodies, immune checkpoint inhibitors, and small-molecule inhibitors, have achieved certain successes. In this review, we summarize the role of macrophages in current immunotherapies and the advantages of targeting macrophages. To better understand and make better use of this type of cell, their development and differentiation characteristics, categories, typical markers, and functions were collated at the beginning of the review. Therapeutic strategies based on or combined with macrophages have the potential to improve the treatment efficacy of cancer therapies.

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Macrophages as a “weapon” in anticancer cellular immunotherapy

The Kaohsiung Journal of Medical Sciences ◽

10.1002/kjm2.12405 ◽

2021 ◽

Author(s):

Dmitry Aminin ◽

Yun‐Ming Wang

Keyword(s):

Cellular Immunotherapy

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Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

Therapeutic Advances in Infectious Disease ◽

10.1177/2049936121991377 ◽

2021 ◽

Vol 8 ◽

pp. 204993612199137

Author(s):

Aditya Jandial ◽

Kundan Mishra ◽

Rajeev Sandal ◽

Kamal Kant Sahu

Keyword(s):

Stem Cell ◽

Platelet Rich Plasma ◽

Severe Disease ◽

Unmet Need ◽

Bk Virus ◽

Haematopoietic Stem Cell ◽

Cellular Immunotherapy ◽

Cell Transplant ◽

Clotting Factors ◽

Haemorrhagic Cystitis

BK virus (BKV)-related haemorrhagic cystitis (HC) is an important cause of morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). The various risk factors include high-level BKV viruria and/or viremia, myeloablative conditioning, acute graft versus host disease (GVHD), cytomegalovirus viremia, and unrelated or HLA-mismatched donor. The presence of high plasma BK viral load and cytopenias have been implicated as important predictors for protracted disease course. These patients frequently require hospitalisation which may extend for several weeks. Supportive measures in the form of analgesics, intravenous hydration, bladder irrigation, and transfusion support remain the mainstay of management. Various drugs have been used with limited success in this setting. These include antiviral drugs, fluoroquinolones, leflunomide, growth factors, clotting factors, estrogens, and prostaglandins. The role of adoptive cellular immunotherapy has also been explored but lacks clinical validation. The strategies aimed at expediting urothelial repair like hyperbaric oxygen therapy (HBOT), intravesical fibrin glue and platelet-rich plasma (PRP) are emerging. Some patients with severe disease do require surgical intervention to relieve urinary obstruction. The frequent co-occurrence of acute GVHD and CMV disease further complicates the management in such patients. There is an unmet need for effective and evidence-based options for the prevention and management of this disease. Due to lack of robust data supported by randomised trials, the acceptability of the available guidelines to simplify the treatment is expected to be low. Despite the availability of various treatment options, the management of BKV-related HC in day-to-day practice continues to be a challenge. The aim of this article is to put forward an up-to-date review of the preventive and therapeutic strategies for BKV-related HC.

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Personalized Immunotherapy Treatment Strategies for a Dynamical System of Chronic Myelogenous Leukemia

Cancers ◽

10.3390/cancers13092030 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2030

Author(s):

Paul A. Valle ◽

Luis N. Coria ◽

Corina Plata

Keyword(s):

Dynamical System ◽

Cancer Cells ◽

Chronic Myelogenous Leukemia ◽

Sufficient Conditions ◽

Treatment Strategies ◽

Myelogenous Leukemia ◽

Invariant Sets ◽

Cellular Immunotherapy ◽

Complete Eradication ◽

Treatment Parameter

This paper is devoted to exploring personalized applications of cellular immunotherapy as a control strategy for the treatment of chronic myelogenous leukemia described by a dynamical system of three first-order ordinary differential equations. The latter was achieved by applying both the Localization of Compact Invariant Sets and Lyapunov’s stability theory. Combination of these two approaches allows us to establish sufficient conditions on the immunotherapy treatment parameter to ensure the complete eradication of the leukemia cancer cells. These conditions are given in terms of the system parameters and by performing several in silico experimentations, we formulated a protocol for the therapy application that completely eradicates the leukemia cancer cells population for different initial tumour concentrations. The formulated protocol does not dangerously increase the effector T cells population. Further, complete eradication is considered when solutions go below a finite critical value below which cancer cells cannot longer persist; i.e., one cancer cell. Numerical simulations are consistent with our analytical results.

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Cellular Immunotherapy Targeting Cancer Stem Cells: Preclinical Evidence and Clinical Perspective

Cells ◽

10.3390/cells10030543 ◽

2021 ◽

Vol 10 (3) ◽

pp. 543

Author(s):

Chiara Donini ◽

Ramona Rotolo ◽

Alessia Proment ◽

Massimo Aglietta ◽

Dario Sangiolo ◽

...

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Indirect Evidence ◽

Cellular Immunotherapy ◽

Preclinical Studies ◽

Clinical Perspective ◽

Antigen Receptors ◽

Chimeric Antigen Receptors ◽

Relevant Issue ◽

Selective Elimination

The term “cancer stem cells” (CSCs) commonly refers to a subset of tumor cells endowed with stemness features, potentially involved in chemo-resistance and disease relapses. CSCs may present peculiar immunogenic features influencing their homeostasis within the tumor microenvironment. The susceptibility of CSCs to recognition and targeting by the immune system is a relevant issue and matter of investigation, especially considering the multiple emerging immunotherapy strategies. Adoptive cellular immunotherapies, especially those strategies encompassing the genetic redirection with chimeric antigen receptors (CAR), hold relevant promise in several tumor settings and might in theory provide opportunities for selective elimination of CSC subsets. Initial dedicated preclinical studies are supporting the potential targeting of CSCs by cellular immunotherapies, indirect evidence from clinical studies may be derived and new studies are ongoing. Here we review the main issues related to the putative immunogenicity of CSCs, focusing on and highlighting the existing evidence and opportunities for cellular immunotherapy approaches with T and non-T antitumor lymphocytes.

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