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Specific Adoptive T-Cell Therapy for Viral and Fungal Infections

ABSTRACT: Despite advances in anti-infective agents, viral and fungal infections after hematopoietic stem cell transplantation (HSCT) continue to cause life-threatening complications that limit the success of HSCT. Early adoptive T-cell immunotherapy studies showed that administration of allogeneic virus-specific cytotoxic T lymphocytes (vCTL) can prevent and control viral infections and reconstitute antiviral immunity to cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Advances in immunobiology, in vitro culture technology, and current good manufacturing practice (cGMP) have provided opportunities for advancing adoptive cell therapy for viral infections: (1) T cells have been expanded targeting multiple pathogens; (2) vCTL production no longer requires viral infection or viral vector transduction of antigen-presenting cells (APCs); (3) the source of lymphocytes is no longer restricted to donors who are immune to the pathogens; (4) naive T cells have been redirected with chimeric antigen receptor T cells (CARTs) or armed with bispecific antibody-armed T cells (BATs) to mediate vCTL activity; (5) these technologies could be combined to targeted multiple viral or fungal pathogens; and (6) pathogen-specific T-cell products manufactured from third parties and banked for “off-the-shelf” use post-HSCT may soon become a reality.

SUBMITTER: Segal B

PROVIDER: S-EPMC7121368 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Project description:Allogeneic stem cell transplantation (alloSCT) is the most robust form of adoptive cellular therapy (ACT) and has been tremendously effective in the treatment of leukemia. It is one of the original forms of cancer immunotherapy and illustrates that lymphocytes can specifically recognize and eliminate aberrant, malignant cells. However, because of the high morbidity and mortality that is associated with alloSCT including graft-versus-host disease (GvHD), refining the anti-leukemia immunity of alloSCT to target distinct antigens that mediate the graft-versus-leukemia (GvL) effect could transform our approach to treating leukemia, and possibly other hematologic malignancies. Over the past few decades, many leukemia antigens have been discovered that can separate malignant cells from normal host cells and render them vulnerable targets. In concert, the field of T-cell engineering has matured to enable transfer of ectopic high-affinity antigen receptors into host or donor cells with greater efficiency and potency. Many preclinical studies have demonstrated that engineered and conventional T-cells can mediate lysis and eradication of leukemia via one or more leukemia antigen targets. This evidence now serves as a foundation for clinical trials that aim to cure leukemia using T-cells. The recent clinical success of anti-CD19 chimeric antigen receptor (CAR) cells for treating patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia displays the potential of this new therapeutic modality. In this review, we discuss some of the most promising leukemia antigens and the novel strategies that have been implemented for adoptive cellular immunotherapy of lymphoid and myeloid leukemias. It is important to summarize the data for ACT of leukemia for physicians in-training and in practice and for investigators who work in this and related fields as there are recent discoveries already being translated to the patient setting and numerous accruing clinical trials. We primarily focus on ACT that has been used in the clinical setting or that is currently undergoing preclinical testing with a foreseeable clinical endpoint.

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Specific Adoptive T-Cell Therapy for Viral and Fungal Infections

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