Targeting tumours with genetically enhanced T lymphocytes

@article{Sadelain2003TargetingTW,
  title={Targeting tumours with genetically enhanced T lymphocytes},
  author={M. Sadelain and I. Rivi{\`e}re and R. Brentjens},
  journal={Nature Reviews Cancer},
  year={2003},
  volume={3},
  pages={35-45}
}
The genetic modification of T lymphocytes is an important approach to investigating normal T-cell biology and to increasing antitumour immunity. A number of genetic strategies aim to increase the recognition of tumour antigens, enhance antitumour activities and prevent T-cell malfunction. T cells can also be engineered to increase safety, as well as to express markers that can be tracked by non-invasive imaging technologies. Genetically modified T cells are therefore proving to be of great… Expand

Figures, Tables, and Topics from this paper

Therapeutic T cell engineering
TLDR
Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape. Expand
Genetic engineering of T cells for adoptive immunotherapy
TLDR
This article focuses on strategies to dissect the signals controlling T cell proliferation; render CD4 T cells resistant to HIV-1 infection; and redirect CD8 T cell antigen specificity. Expand
Engineered T cells for anti-cancer therapy.
TLDR
Clinical studies of genetically modified T cell therapy for cancer have shown notable success; however, these trials demonstrate that tumor therapy with engineered high avidity tumor-reactive T cells may be accompanied by significant on-target toxicity, necessitating careful selection of target antigens and development of strategies to eliminate transferred cells. Expand
Genetic modification of T cells for immunotherapy
TLDR
The rationale for genetic modification of T cells, the critical steps involved in gene transfer, and potential advantages and disadvantages of strategies that are now being examined to engineer improved effector T cells for the treatment of human infectious and malignant disease are discussed. Expand
Genetically Engineered Antigen Specificity in T Cells for Adoptive Immunotherapy
TLDR
The advantage of the adoptive transfer of modified T cells over immunotherapies developed to date such as vaccines or cytokines alone is that T cells have the ability to directly traffic to the site of tumor or infection, to multiply at that site, and to persist in a memory state for months to years. Expand
Adoptive T cell therapy for cancer in the clinic.
  • C. June
  • Medicine
  • The Journal of clinical investigation
  • 2007
TLDR
The transfusion of lymphocytes, referred to as adoptive T cell therapy, is being tested for the treatment of cancer and chronic infections and the current status of the field and prospects for clinical translation are reviewed herein. Expand
Producing proT cells to promote immunotherapies
T lymphocytes are critical mediators of the adaptive immune system and they can be harnessed as therapeutic agents against pathogens and in cancer immunotherapy. T cells can be isolated and expandedExpand
Genetic redirection of T cells for cancer therapy
TLDR
Recent advances in the genetic modification of T cells using genes encoding cell‐surface receptors specific for tumor‐associated antigen are described and details of the progress in clinical application are provided. Expand
Gene modification strategies to induce tumor immunity.
TLDR
How many diverse cell types, including dendritic cells, T cells, and tumor cells, are being modified with a variety of genes, including those encoding antigens, cytokines, and chemokines, in order to enhance tumor immunity is described. Expand
RORing T cells target CLL and MCL.
TLDR
Patients' peripheral blood T cells can be readily redirected toward any chosen antigen, including tumor antigens, and infused to promptly raise the number of tumor-reactive T cells without requiring active immunization and without the risk of deleterious alloreactivity. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 168 REFERENCES
Progress in human tumour immunology and immunotherapy
TLDR
Clinical studies using immunization with peptides derived from cancer antigens have shown that high levels of lymphocytes with anti-tumour activity can be raised in cancer-bearing patients. Expand
Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells.
Publisher Summary This chapter attempts to identify the principles and issues elucidated in animal models that may provide insights for the development of effective approaches to modulate T cellExpand
Expansion and characterization of T cells transduced with a chimeric receptor against ovarian cancer.
TLDR
These studies establish the feasibility of consistently generating large numbers of gene-modified tumor-reactive lymphocytes, with a stable and diverse cytokine repertoire, that could be utilized for patient treatment. Expand
Activation conditions determine susceptibility of murine primary T‐lymphocytes to retroviral infection
TLDR
This work has shown that retroviral‐mediated gene transfer into murine primary T‐cells has remained elusive and the definition of factors controlling Retroviral infection of T‐lymphocytes would also be useful to better understand retrovirus diseases. Expand
Implications for immunosurveillance of altered HLA class I phenotypes in human tumours.
TLDR
Altered HLA class I tumour phenotypes are analyzed in detail, indicating their potential relevance for implementation of immunotherapeutic protocols and strategies to overcome tumour escape mechanisms. Expand
Costimulatory approaches to adoptive immunotherapy.
TLDR
This review examines approaches, including ex vivo T-cell expansion, systemic "delivery" of constimulation, tumors transduced or transfected with costimulatory ligands, and vaccine strategies using coimmunization with the genes for costimulation ligands. Expand
Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes
TLDR
The adoptive transfer of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen resulted in the persistent clonal repopulation of T cells in cancer patients, leading to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. Expand
Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides
We describe functional simplified T cell and Fc receptor chimeras that are capable of directing CD8+ cytotoxic T lymphocytes (CTLs) to specifically recognize and lyse cells expressing HIV envelopeExpand
CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy.
TLDR
Newly emerging data suggest that inhibitory signals mediated by CTLA-4 not only can determine whether T cells become activated, but also can play a role in regulating the clonal representation in a polyclonal response. Expand
Immunotherapy through TCR gene transfer
TLDR
The genetic introduction of a virus-specific TCR into peripheral T cells in a mouse model system showed that T cells redirected by TCR gene transfer expanded upon viral infection of mice and efficiently homed to effector sites, suggesting that the redirection of T cells by T CR gene transfer is a viable strategy for the rapid induction of virus- or tumor-specific immunity. Expand
...
1
2
3
4
5
...