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Synthetic immunology: T-cell engineering and adoptive immunotherapy.

ABSTRACT: During the past decades, the rapidly-evolving cancer is hard to be thoroughly eliminated even though the radiotherapy and chemotherapy do exhibit efficacy in some degree. However, a breakthrough appeared when the adoptive cancer therapy [1] was developed, especially T cells armed with chimeric antigen receptors (CARs) showed great potential in tumor clinical trials recently. CAR-T cells successfully elevated the efficiency and specificity of cytotoxicity. In this review, we will talk about the design of CAR and CAR-included combinatory therapeutic applications in the principles of systems and synthetic immunology.

SUBMITTER: Si W

PROVIDER: S-EPMC6190530 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Synthetic immunology: T-cell engineering and adoptive immunotherapy.

Si Wen W Li Cheng C Wei Ping P

Synthetic and systems biotechnology 20180901 3

During the past decades, the rapidly-evolving cancer is hard to be thoroughly eliminated even though the radiotherapy and chemotherapy do exhibit efficacy in some degree. However, a breakthrough appeared when the adoptive cancer therapy [1] was developed, especially T cells armed with chimeric antigen receptors (CARs) showed great potential in tumor clinical trials recently. CAR-T cells successfully elevated the efficiency and specificity of cytotoxicity. In this review, we will talk about the d ...[more]

PMID: 30345403

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Project description:Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapeutic option for a wide range of immune and hematologic malignant and non-malignant disorders. Once transplanted, allogeneic cells have to support myeloid repopulation and immunological reconstitution, but also need to become tolerant to the host via central or peripheral mechanisms to achieve the desired therapeutic effect. Peripheral tolerance after allogeneic HSCT may be achieved by several mechanisms, though blocking alloreactivity to the host human leukocyte antigens while preserving immune responses to pathogens and tumor antigens remains a challenge. Recently uncovered evidence on the mechanisms of post-HSCT immune reconstitution and tolerance in transplanted patients has allowed for the development of novel cell-based therapeutic approaches. These therapies are aimed at inducing long-term peripheral tolerance and reducing the risk of graft-vs-host disease (GvHD), while sparing the graft-vs-leukemia (GvL) effect. Thus, ensuring effective long term remission in hematologic malignancies. Today, haploidentical stem cell transplants have become a widely used treatment for patients with hematological malignancies. A myriad of ex vivo and in vivo T-cell depletion strategies have been adopted, with the goal of preventing GvHD while preserving GvL in the context of immunogenetic disparity. αβ T-cell/CD19 B-cell depletion techniques, in particular, has gained significant momentum, because of the high rate of leukemia-free survival and the low risk of severe GvHD. Despite progress, better treatments are still needed in a portion of patients to further reduce the incidence of relapse and achieve long-term tolerance. Current post-HSCT cell therapy approaches designed to induce tolerance and minimizing GvHD occurrence include the use of (i) γδ T cells, (ii) regulatory Type 1 T (Tr1) cells, and (iii) engineered FOXP3+ regulatory T cells. Future protocols may include post-HSCT infusion of allogeneic effector or regulatory T cells engineered with a chimeric antigen receptor (CAR). In the present review, we describe the most recent advances in graft engineering and post-HSCT adoptive immunotherapy.

Dataset Information

Synthetic immunology: T-cell engineering and adoptive immunotherapy.

Publications

Synthetic immunology: T-cell engineering and adoptive immunotherapy.

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