Virus specific car t cells

Despite decades of research and the best up-to-date treatments, grade 4 Glioblastoma (GBM) remains uniformly fatal with a patient median overall survival of less than 2 years. Recent advances in immunotherapy have reignited interest in utilizing immunological approaches to fight cancer. However, current immunotherapies have so far not met the anticipated expectations, achieving modest results in their journey from bench to bedside for the treatment of GBM. Understanding the intrinsic features of GBM is of crucial importance for the development of effective antitumoral strategies to improve patient life expectancy and conditions...

Oncolytic virus (OV) therapy has emerged as a promising frontier in cancer treatment, especially for solid tumours. While immunotherapies like immune checkpoint inhibitors and CAR-T cells have demonstrated impressive results, their limitations in inducing complete tumour regression have spurred researchers to explore new approaches targeting tumours resistant to current immunotherapies. OVs, both natural and genetically engineered, selectively replicate within cancer cells, inducing their lysis while sparing normal tissues...

Cancer is one of the most devastating complications of kidney transplantation and constitutes one of the leading causes of morbidity and mortality among solid organ transplantation (SOT) recipients. Immunosuppression, although effective in preventing allograft rejection, inherently inhibits immune surveillance against oncogenic viral infections and malignancy. Adoptive cell therapy, particularly immune effector cell therapy, has long been a modality of interest in both cancer and transplantation, though has only recently stepped into the spotlight with the development of virus-specific T-cell therapy and chimeric antigen receptor T-cell therapy...

BACKGROUND: Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. METHODS: Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells...

PURPOSE OF THE REVIEW: The central nervous system (CNS) is an hotspot for HIV persistence and may be a major obstacle to overcome for curative strategies. The peculiar anatomical, tissular and cellular characteristics of the HIV reservoir in the CNS may need to be specifically addressed to achieve a long-term HIV control without ART. In this review, we will discuss the critical challenges that currently explored curative strategies may face in crossing the blood-brain barrier (BBB), targeting latent HIV in brain-resident myeloid reservoirs, and eliminating the virus without eliciting dangerous neurological adverse events...

Malignant melanoma is the most aggressive form of skin cancer. Standard treatment options include surgery, radiation therapy, systemic chemotherapy, targeted therapy, and immunotherapy. Combining these modalities often yields better responses. Surgery is suitable for localized cases, sometimes involving lymph node dissection and biopsy, to assess the spread of the disease. Radiation therapy may be sometimes used as a standalone treatment or following surgical excision. Systemic chemotherapy, while having low response rates, is utilized as part of combination treatments or when other methods fail...

Efficient T cell engineering is central to the success of CAR T cell therapy but involves multiple time-consuming manipulations, including T cell isolation, activation, and transduction. These steps add complexity and delay CAR T cell manufacturing, which takes a mean time of 4 weeks. To streamline T cell engineering, we strategically combine two critical engineering solutions - T cell-specific lentiviral vectors and macroporous scaffolds - that enable T cell activation and transduction in a simple, single step...

Immunotherapy has emerged as a revolutionary approach in cancer therapy, and recent advancements hold significant promise for breast cancer (BCa) management. Employing the patient's immune system to combat BCa has become a focal point in immunotherapeutic investigations. Strategies such as immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT), and targeting the tumor microenvironment (TME) have disclosed encouraging clinical outcomes. ICIs, particularly programmed cell death protein 1 (PD-1)/PD-L1 inhibitors, exhibit efficacy in specific BCa subtypes, including triple-negative BCa (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive cancers...

In this article, we discuss a recently published article that demonstrated a novel way of identifying viral pathogens reactivating in human cells to be used as cellular therapy, in this instance chimeric antigen receptor (CAR) T cells. The authors used search engines and databases to identify viruses able to reactivate in T cells and then tested this initially in T-cell cultures, specifically human herpesvirus 6. This virus was then shown to reactivate infrequently in vitro and in vivo in CAR T cells as a consequence of T-cell activation...

Current treatments for T cell malignancies encounter issues of disease relapse and off-target toxicity. Using T cell receptor (TCR)Vβ2 as a model, here we demonstrate the rapid generation of an off-the-shelf allogeneic chimeric antigen receptor (CAR)-T platform targeting the clone-specific TCR Vβ chain for malignant T cell killing while limiting normal cell destruction. Healthy donor T cells undergo CRISPR-induced TRAC, B2M and CIITA knockout to eliminate T cell-dependent graft-versus-host and host-versus-graft reactivity...

BACKGROUND: CAR-T cells targeting the B-cell antigen CD19 are standard therapy for relapsed/ refractory B-cell lymphoma and leukemia. CAR-T cell therapy in solid tumors is limited due to an immunosuppressive tumor microenvironment (TME) and a lack of tumor-restricted antigens. We recently engineered an oncolytic virus (CF33) with high solid tumor affinity and specificity to deliver a non-signaling truncated CD19 antigen (CD19t), allowing targeting by CD19-CAR-T cells. Here, we tested this combination against pancreatic cancer...

Development of successful cancer therapeutics requires exploration of the differences in genetics, metabolism, and interactions with the immune system among malignant and normal cells. The clinical observation of spontaneous tumor regression following natural infection with microorganism has created the premise of their use as cancer therapeutics. Oncolytic viruses (OVs) originate from viruses with attenuated virulence in humans, well-characterized vaccine strains of known human pathogens, or engineered replication-deficient viral vectors...

Precision immune oncology capitalizes on identifying and targeting tumor-specific antigens to enhance anti-tumor immunity and improve the treatment outcomes of solid tumors. Gastric cancer (GC) is a molecularly heterogeneous disease where monoclonal antibodies against human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death 1 (PD-1) combined with systemic chemotherapy have improved survival in patients with unresectable or metastatic GC. However, intratumoral molecular heterogeneity, variable molecular target expression, and loss of target expression have limited antibody use and the durability of response...

Glioblastoma (GBM), the most common primary brain tumor in adults, is characterized by low survival rates and a grim prognosis. Current treatment modalities, including extensive surgical resection, chemotherapy, and radiation therapy, often yield limited success due to the brain's sensitivity, leading to significant side effects. Exciting advancements in immunotherapy have recently shown promise in treating various types of tumors, raising hopes for improved outcomes in brain tumor patients. One promising immunotherapy approach is chimeric antigen receptor (CAR) T-cell therapy, which recognizes surface proteins on targeted tumor cells and redirects cytotoxicity towards specific targets...

Genetically modified macrophage infusion has been proven to be a novel treatment for cancer. One of the most important processes in macrophage-based therapy is the efficient transfer of genes. HIV-1-derived lentiviruses were widely used as delivery vectors in chimeric antigen receptor T and NK cell construction. While macrophages are relatively refractory to this lentiviral vector transduction as a result of the myeloid-specific restriction factor SAMHD1, which inhibited the virion cycle through exhausting the dNTPs pool and degradating RNAs...

Natural killer (NK)/T cell lymphoma (NKTCL) is a rare subtype of Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma characterized by poor clinical outcomes. It is more common in East Asian and Latin American countries. Despite the introduction of asparaginase/pegaspargase-based chemotherapy, the prognosis of patients with advanced NKTCL needs to be improved, and few salvage treatment options are available for relapsed/refractory patients who fail chemotherapy. Although many unknowns remain, novel treatment strategies to further improve outcomes are urgently needed...

Head and neck squamous cell carcinoma (HNSCC) is a major challenge for current therapies. CAR-T cells have shown promising results in blood cancers, however, their effectiveness against solid tumors remains a hurdle. Recently, CD44v6-directed CAR-T cells demonstrated efficacy in controlling tumor growth in multiple myeloma and solid tumors such as HNSCC, lung and ovarian adenocarcinomas. Apart from CAR-T cells, CAR-NK cells offer a safe and allogenic alternative to autologous CAR-T cell therapy. In this paper, we investigated the capacity of CAR-NK cells redirected against CD44v6 to execute cytotoxicity against HNSCC...

Adoptive cell therapy (ACT) has transformed the treatment landscape for cancer and infectious disease through the investigational use of chimeric antigen receptor T-cells (CAR-Ts), tumour-infiltrating lymphocytes (TILs) and viral-specific T-cells (VSTs). Whilst these represent breakthrough treatments, there are subsets of patients who fail to respond to autologous ACT products. This is frequently due to impaired patient T-cell function or "fitness" as a consequence of prior treatments and age, and can be exacerbated by complex manufacturing protocols...

The efficacy of therapeutic T-cells is limited by a lack of positive signals and excess inhibitory signaling in tumor microenvironments. We previously showed that a constitutively active IL7 receptor (C7R) enhanced the persistence, expansion, and anti-tumor activity of T-cells expressing chimeric antigen receptors (CARs), and C7R-modified GD2.CAR T-cells are currently undergoing clinical trials. To determine if the C7R could also enhance the activity of T-cells recognizing tumors via their native T-cell receptors (TCRs), we evaluated its effects in Epstein-Barr virus (EBV)-specific T-cells (EBVSTs) that have produced clinical benefits in patients with EBV-associated malignancies...

Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited...